中药有效成分抗宫颈癌作用机制的研究进展
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摘要
宫颈癌是威胁女性健康的第二大癌症,因其极高的死亡率而备受国内外研究者的关注。目前,大多采用放射性治疗及化学药物治疗癌症的副作用较大,而中药有效成分在抗肿瘤方面有着多途径、多环节、多靶点、毒副作用小等优势,已成为抗癌药物的重点研发对象。近年来,相关科研人员对中药有效成分作用于人宫颈癌细胞的体外抑制活性及作用机制研究尤为活跃。文章拟从中药提取物、多糖、生物碱、皂苷、黄酮类、萜类、醌类、挥发油、酯类、酚类、砷剂类、蛋白组分等中药有效成分为出发点,以抗宫颈癌作用机制即抑制细胞增殖,诱导癌细胞凋亡;抑制细胞侵袭、迁移及黏着斑激酶(FAK)磷酸化;抑制血管内皮生长因子(VEGF)过表达;干扰细胞有丝分裂;抑制端粒酶活性;调节细胞信号通路;下调HPV E6基因表达;调节机体免疫能力为主要内容,对宫颈癌细胞的体外抑制活性与作用机制进行综述,以期为抗宫颈癌药物的研发与利用提供理论参考。
Cervical cancer is the second cancer that threatens women' s health,and has attracted the attention of researchers at home and abroad because of its extremely high mortality rate. At present,most of the radiotherapy methods and chemical drugs for cancer treatment have serious side effects,and the active ingredients of traditional Chinese medicine have become the key research and development targets of anti-cancer drugs due to many advantages,such as multi-channel,multi-link,multi-target,and less toxicity. In recent years,researchers have been particularly active in researching the inhibitory activity and mechanism of active ingredients of traditional Chinese medicine for human cervical cancer cells. In this paper,the inhibitory activity and mechanism of traditional Chinese medicine against human cervical cancer cells were investigated from crude extract of traditional Chinese medicine,polysaccharides,alkaloids,saponins,flavonoids,terpenoids,quinones,volatile oils,esters,phenols,arsenical,protein components as the starting point; anti-cervical cancer mechanism was investigated,such as inhibiting cell proliferation inducing apoptosis of cancer cells,inhibiting cell invasion,migration and focal adhesion kinase( FAK) phosphorylation,inhibiting vascular endothelial growth factor( VEGF)over-expression interfering with cell mitosis,inhibiting Granzyme activity,regulating cellular signaling pathway,down-regulating HPV E6 gene expression,and regulating immune function. Its in vitro inhibitory activity and mechanism of action on cervical cancer cells were reviewed,in order to provide a theoretical basis for the development and utilization of anti-cervical cancer drugs.
Cervical cancer is the second cancer that threatens women' s health,and has attracted the attention of researchers at home and abroad because of its extremely high mortality rate. At present,most of the radiotherapy methods and chemical drugs for cancer treatment have serious side effects,and the active ingredients of traditional Chinese medicine have become the key research and development targets of anti-cancer drugs due to many advantages,such as multi-channel,multi-link,multi-target,and less toxicity. In recent years,researchers have been particularly active in researching the inhibitory activity and mechanism of active ingredients of traditional Chinese medicine for human cervical cancer cells. In this paper,the inhibitory activity and mechanism of traditional Chinese medicine against human cervical cancer cells were investigated from crude extract of traditional Chinese medicine,polysaccharides,alkaloids,saponins,flavonoids,terpenoids,quinones,volatile oils,esters,phenols,arsenical,protein components as the starting point; anti-cervical cancer mechanism was investigated,such as inhibiting cell proliferation inducing apoptosis of cancer cells,inhibiting cell invasion,migration and focal adhesion kinase( FAK) phosphorylation,inhibiting vascular endothelial growth factor( VEGF)over-expression interfering with cell mitosis,inhibiting Granzyme activity,regulating cellular signaling pathway,down-regulating HPV E6 gene expression,and regulating immune function. Its in vitro inhibitory activity and mechanism of action on cervical cancer cells were reviewed,in order to provide a theoretical basis for the development and utilization of anti-cervical cancer drugs.
引文
[1] Ferlay J,Soerjomataram I,Dikshit R,et al. Cancer incidenceand mortality worldwide:sources,methods and major patterns inGLOBOCAN 2012[J]. Int J Cancer,2015,136(5):E359.
[2]于浩,杜建玲.穿山龙皂苷的药理作用及机制的研究现状[J].中国中药杂志,2017,42(24):4694.
[3]程丽艳,屠凌岚,史红.p38MAPK对慢性前列腺炎疼痛的影响及槲皮素的干预作用[J].中国现代应用药学,2016,33(8):984.
[4]陈娜,杨滨.西红花非药用部位化学成分和药理作用研究进展[J].中国中药杂志,2018,43(14):2884.
[5]尤良震,林逸轩,方朝晖,等.黄芪甲苷治疗糖尿病及其并发症药理作用研究进展[J].中国中药杂志,2017,42(24):4700.
[6]万英洁,夏建新,唐丽.新疆一枝蒿化学成分、药理作用及临床应用研究进展[J].中国中药杂志,2017,42(23):4565.
[7]陈影,陈两绵,仝燕,等.山豆根药理毒理研究进展[J].中国中药杂志,2017,42(13):2439.
[8]张旻昱,吴宏伟,许利平,等.五味子及其活性成分治疗心脑血管疾病药理作用的研究进展[J].中国中药杂志,2018,43(8):1536.
[9]曾婧,王芳.中药及其单体治疗HPV感染宫颈癌的研究进展[J].西北药学杂志,2015,30(3):318.
[10]何秀霞,张春兰,何乃彦,等.独角莲提取液体外抗宫颈癌He La细胞增殖和诱导凋亡的研究[J].时珍国医国药,2011,22(7):1620.
[11]李鑫,于波,张素霜,等.甘草提取物(GC-X)体外诱导人宫颈癌He La细胞凋亡作用的研究[J].黑龙江畜牧兽医,2016(6):198.
[12]王晓华,尹元琴,马萍,等.骆驼蓬全草提取物的抗肿瘤作用[J].沈阳药科大学学报,2006,23(8):534.
[13]赵相轩.水龙骨提取物对宫颈癌He La细胞增殖和凋亡的影响[J].临床肿瘤学杂志,2018,23(2):122.
[14]贺海波,白彩虹,石孟琼,等.威灵仙不同部位对人宫颈癌CaSKi细胞增殖抑制作用实验研究[C].北京:2012全国临床中药学学术研讨会,2012.
[15]范鹏莺.夏枯草提取物对人乳头瘤病毒阳性宫颈癌细胞的凋亡作用[J].药物评价研究,2016,39(3):388.
[16]李桂玲,归绥琪,王莉,等.掌叶半夏有效提取物对He La细胞的作用及机制[J].中国中西医结合杂志,2010,30(3):303.
[17]葛文静,段冷昕,刘玲,等.壁虎醇提物抑制人宫颈癌SiHa细胞迁移及侵袭的研究[J].中国临床药理学杂志,2016,32(10):913.
[18]周永芹,韩莉.蜈蚣提取物对宫颈癌Caski细胞增殖的抑制效应[J].中国组织工程研究,2007,11(34):6805.
[19]杨培民,代龙,李钦青,等.白花蛇舌草多糖对人宫颈癌He La细胞和人肝癌Bel-7402细胞生长的影响[J].现代中药研究与实践,2010(3):32.
[20]靳祎,肖锋,武均宜,等.刺五加多糖下调Survivin蛋白表达诱导He La细胞凋亡[J].中成药,2016,38(4):902.
[21] Cao W,Li X Q,Wang X,et al. A novel polysaccharide,isolatedfrom Angelica sinensis(Oliv.)diels induces the apoptosis of cervi-cal cancer He La cells through an intrinsic apoptotic pathway[J].Phytomedicine,2010,17(8/9):598.
[22]杨婧,戚基萍,王锐,等.红花多糖对人宫颈癌He La细胞增殖和VEGF表达的影响[J].中国实验方剂学杂志,2016(8):111.
[23]姜恩平,王卓,陈建光,等. ERK信号途径介导五味子多糖对He La细胞凋亡和侵袭的作用[J].时珍国医国药,2015(8):1892.
[24]杨滨,娄晓明,吴春丽,等.银杏外种皮多糖对人宫颈癌细胞系Siha增殖及侵袭的影响[J].实用药物与临床,2011,14(3):179.
[25]周聪,孙月,李德海,等.柳蘑多糖对肿瘤细胞增殖抑制作用的研究[J].现代食品科技,2017,33(9):56.
[26]魏士杰,陈文强.云芝子实体多糖对人宫颈癌He La细胞生长和凋亡的影响研究[J].四川大学学报:自然科学版,2016,53(5):1162.
[27] Jose G M,Kurup G M. Sulfated polysaccharides from Padina tet-rastromatica arrest cell cycle,prevent metastasis and downregulateangiogenic mediators in He La cells[J]. Bioactive Carbohydrates&Dietary Fibre,2017,12:7.
[28]贾艳菊,代玲,张灿.龙葵生物碱诱导He La细胞凋亡的研究[J].动物医学进展,2010,31(8):51.
[29]张培,王海琳,张恒亮,等.苦参碱对宫颈癌SiHa细胞增殖的抑制作用及JAK-STAT信号通路的影响[J].现代肿瘤医学,2014,22(8):1790.
[30]狄晓鸿,高英敏,郭红云.黄连素对人宫颈癌He La细胞株的体外作用研究[J].中国中医药信息杂志,2008,15(1):30.
[31]王远兴,贾素花,曾雯瑜,等.卵叶娃儿藤生物碱对宫颈癌细胞株He La的体外作用[J].食品科学,2008,29(11):609.
[32]刘诗伶.去氢骆驼蓬碱对宫颈癌的抑制作用及其分子机制研究[D].南昌:南昌大学,2018.
[33]张莹,张起辉,吴立军,等.吴茱萸碱诱导人宫颈癌He La细胞凋亡过程中非caspase调控因素[J].中国药理学通报,2004,20(1):61.
[34]周斌,于世英.羟基喜树碱对宫颈癌He La细胞的放射增益作用及影响因素的研究[J].华中科技大学学报:医学版,2006,35(3):396.
[35]张如松,叶益萍.白首乌甾体总苷的体外抗肿瘤作用[J].中草药,2000,31(8):599.
[36]刘志华,王刚,沈建飞.柴胡皂苷-D抑制宫颈癌He La细胞的分子机制研究[J].中华中医药学刊,2016,34(12):2931.
[37]李文,旷雨,孟立峰,等.黄芪甲苷对宫颈癌He La细胞增殖、迁移侵袭作用机制研究[J].中药药理与临床,2018,34(3):39.
[38]高苗,刘娟娟,王栋.绞股蓝总皂苷对宫颈癌He La细胞的生长抑制作用及可能的分子机制[J].肿瘤,2013,33(10):868.
[39]熊明华.人参皂苷Rg3对人宫颈癌He La细胞凋亡及Bcl-2/bax基因mRNA表达的影响[J].中国现代医学杂志,2012,22(3):34.
[40]程卉,苏婧婧,候会洁,等.重楼皂苷Ⅰ抗宫颈癌He La细胞作用及机制研究[J].中药材,2013,36(11):1815.
[41]张文秀.薯蓣皂苷元对人宫颈癌细胞增殖的影响[J].中国现代医生,2011,49(26):5.
[42]徐敏,卜平,李瑶瑶.半枝莲黄酮类化合物对体外肿瘤血管生成的影响[J].世界华人消化杂志,2007,15(20):2215.
[43]吾热娅提古丽·克维尔,艾百拉·热合曼,胡尼其古丽·阿巴克,等.蜂胶黄酮短叶松素-3-乙酸酯对人宫颈癌SiHa和大肠癌HT29细胞增殖及凋亡的影响[J].中国新药杂志,2016,25(24):2881.
[44]胡艳玲,李国利,林中翔.葛根素对人宫颈癌He La细胞体外增殖的影响及机制研究[J].中国地方病防治杂志,2017,32(12):1427.
[45]惠双.黄芩苷对宫颈癌细胞株He La的放射增敏作用[J].中国病理生理杂志,2015,31(12):2126.
[46]陈淑梅.高良姜素诱导人乳头瘤病毒阳性的宫颈癌细胞凋亡实验研究[J].中草药,2017,48(5):941.
[47] Wang Hong,Chen Gu,Guo Xinbo,et al.Influence of the stage ofripeness on the phytochemical profiles,antioxidant andantiprolif-erative activities in different parts of Citrus reticulata Blanco cv.Chachiensis[J]. Lwt-Food Sci Te,2016,69:67.
[48]刘心平,徐文弟.银杏叶黄酮提取工艺及对He La细胞Bcl-2mRNA表达的影响[J].哈尔滨医科大学学报,2005,39(3):250.
[49]孙杰,王芍,郭斌,等.三棱黄酮抗He La宫颈癌:降低分裂期细胞比率诱导细胞凋亡[J].食品科学,2011,32(1):210.
[50]崔侨,田代真一,小野寺敏,等.冬凌草甲素通过诱导人宫颈癌He La细胞自噬下调凋亡的机制[J].药学学报,2007,42(1):35.
[51]程齐来,喻亚飞,李映辰,等.藤梨根中乌苏烷三萜化合物A对宫颈癌He La细胞增殖的影响[J].中国实验方剂学杂志,2015,21(24):84.
[52]刘发英,邹阳,杨必成,等.莪术醇对人宫颈癌SiHa和HCC94细胞增殖、自噬及凋亡的影响[J].中药药理与临床,2018,34(1):62.
[53]张巍,秦迎新,李妍,等.胡桃醌诱导宫颈癌Caski细胞凋亡作用[J].中国公共卫生,2014,30(10):1279.
[54]张巍,吴亚猛,陈思瑶,等.胡桃醌对宫颈癌Si Ha细胞增殖及细胞周期的影响[J].吉林大学学报:医学版,2015,41(4):697.
[55]郝臻凤,刘静,张瑜,等.紫草素对宫颈癌He La细胞增殖、侵袭和迁移的影响[J].中国实验方剂学杂志,2015,21(6):91.
[56]张雪青,邵邻相,吴文才,等.白术挥发油抑菌及抗肿瘤作用研究[J].浙江师范大学学报:自然科学版,2016,39(4):436.
[57]邹辉,杨郴,易美玲,等.白术化学成分分离鉴定[J].中国实验方剂学杂志,2016,22(17):43.
[58] Wang J,Lu J,Lv C,et al. Three new triterpenoid saponins fromroot of Gardenia jasminoides Ellis[J]. Fitoterapia,2012,83(8):1396.
[59]韩苏夏,朱青,杜蓓茹,等.薏苡仁酯诱导人宫颈癌He La细胞凋亡的实验研究[J].肿瘤,2002,22(6):481.
[60]戴彦迪,王玉姝,周晓棉,等.蟾酥脂质体注射液的抗肿瘤作用[J].沈阳药科大学学报,2007,24(9):568.
[61]赵俊云,杨晓敏,郭健.丹皮酚抑制SiHa细胞增殖及COX-2转录的实验研究[J].中医药学报,2016,44(1):52.
[62]夏明钰,王敏伟,田代真一,等.厚朴酚通过改变Bax/Bcl-XL表达和激活caspase诱导人宫颈癌He La细胞凋亡[J].中国药理学通报,2005,21(3):318.
[63]邹姝姝,肖琴,李亚妹,等.苏木总酚对宫颈癌细胞的作用[J].重庆理工大学学报:自然科学,2010,24(3):33.
[64]潘纪红,王海滨,杜晓飞,等.虎杖苷通过P13K/AKT/m TOR信号通路诱导人宫颈癌细胞凋亡的初步研究[J].中国中药杂志,2017,42(12):2345.
[65] Yu J,Qian H,Li Y,et al. Arsenic trioxide(As2O3)reduces theinvasive and metastatic properties of cervical cancer cells in vitroand in vivo[J]. Gynecol Oncol,2007,106(2):400.
[66]林晨,拉莱·苏祖克,史永华,等.三氧化二砷对裸鼠宫颈癌移植瘤的作用及机制[J].肿瘤防治研究,2011,38(4):369.
[67]尹伶,濮德敏,韦立蓓,等. As4S4诱导宫颈癌He La细胞凋亡及对端粒酶活性的影响[J].中国现代医学杂志,2008,18(3):298.
[68]谢江碧,贺卫国,翁宁,等.蚯蚓中抗肿瘤蛋白组分的提取分离及其抗肿瘤活性[J].中国生物化学与分子生物学报,2003,19(3):359.
[69]李兴暖,牛力,赵勇.地鳖虫纤溶活性蛋白组分抑制肿瘤作用研究[J].时珍国医国药,2011,22(5):1149.
[70]孔赛,韩凤娟,张志刚.中药抗宫颈癌HPV感染的研究进展[J].世界中西医结合杂志,2014,9(3):319.
[71]李桂玲,夏晴,陈松华,等.掌叶半夏提取物的有效部位对宫颈癌细胞株HPVE6和P53基因表达的影响[J].中华中医药杂志,2012(1):110.
[72] Jiang E,Sun X,Kang H,et al. Dehydrocostus lactone inhibitsproliferation,antiapoptosis,and invasion of cervical cancer cellsthrough PI3K/Akt signaling pathway[J]. Int J Gynecol Cancer,2015,25(7):1179.
[73] Munagala R,Aqil F,Jeyabalan J,et al. TanshinoneⅡAinhibitsviral oncogene expression leading to apoptosis and inhibition ofcervical cancer[J]. Cancer Lett,2015,356(2):536.
[74] Kaufmann S H,Earnshaw W C. Induction of apoptosis by cancerchemotherapy[J]. Exp Cell Res,2000,256(1):42.
[75] Leblanc A C. Natural cellular inhibitors of caspases[J]. ProgNeuropsychopharmacol Biol Psychiatry,2003,27(2):215.
[76]许立,李霞,张茶,等.东北红豆杉中19种单体化合物对宫颈癌He La细胞增殖的影响[J].武警医学,2011,22(6):513.
[77]贾慧敏,张祖珣,张海燕,等.蚯蚓组织中抑制肿瘤细胞生长物质的分离提取及其作用机制初探[J].肿瘤,2003,23(6):481.
[78] Lipfert L,Haimovich B,Schaller M D,et al. Integrin-dependentphosphorylation and activation of the protein tyrosine kinasepp125FAK in platelets.[J]. J Cell Bio,1992,119(4):905.
[79] Sulzmaier F J,Jean C,Schlaepfer D D. FAK in cancer:mecha-nistic findings and clinical applications[J]. Nat Rev Cancer,2014,14(9):598.
[80] Hsueh C,Lin J D,Wu I C,et al. Vascular endothelial growthfactors and angiopoietins in presentations and prognosis of papilla-ry thyroid carcinoma[J]. J Surg Oncol,2011,103(5):395.
[81] Park J H,Park K J,Kim Y S,et al. Serum angiopoietin-2 as aclinical marker for lung cancer[J]. Chest,2007,132(1):200.
[82] Yalcin M,Dyskin E,Lansing L,et al. Tetraiodothyroacetic acid(tetrac)and nanoparticulate tetrac arrest growth of medullary car-cinoma of the thyroid.[J]. J Clin Endocr Metab,2010,95(4):1972.
[83] Wray C J,Rilo H L,Ahmad S A. Colon cancer angiogenesis andantiangiogenic therapy[J]. Expert Opin Inv Drug,2004,13(6):631.
[84]王立岩,许晓艳,盛敏佳,等. HIF-1α及VEGF在宫颈癌组织中的表达及其临床意义[J].中国实验诊断学,2009,13(12):1749.
[85]周吉华,张庆华.灵芝孢子对老年宫颈癌患者外周血T淋巴细胞亚群及VEGF的影响[J].中国妇幼保健,2014,29(13):2021.
[86]余杰,杨振国,陈美珍,等.牡蛎活性肽体外诱导He La细胞凋亡及其作用机制[J].食品科学,2012,33(21):290.
[87] Shay J W,Wright W E. Role of telomeres and telomerase in canc-er[J].Eur J Cancer,2011,21(6):349.
[88] Günes C,Rudolph K L. The role of telomeres in stem cells andcancer.[J]. Cell,2013,152(3):390.
[89]刘晶,周天兴,刘蕊,等.大黄素对宫颈癌He La细胞端粒损伤作用的研究[J].中国细胞生物学学报,2018,40(2):178.
[90] Nüssleinvolhard C,Wieschaus E. Mutations affecting segmentnumber and polarity in drosophila[J]. Nature, 1980, 287(5785):795.
[91] Krieghoff E,Behrens J,Mayr B. Nucleo-cytoplasmic distributionof beta-catenin is regulated by retention[J]. J Cell Sci,2006,119(7):1453.
[92] Green D R,Reed J C. Mitochondria and apoptosis[J]. Science,1998,281(5381):1309.
[93] Tan K O,Fu N S,Chan S L,et al. MAP1 is a mitochondrial ef-fector of Bax[J]. Proc Natl Acad Sci USA,2005,102(41):14623.
[94] Garrido C,Galluzzi L,Brunet M,et al. Mechanisms of cyto-chrome c release from mitochondria[J]. Cell Death Differ,2006,13(9):1423.
[95] Hengartner M O. The biochemistry of apoptosis[J]. Nature,2000,407(6805):770.
[96]王耀先,郝慧南,陈秀玮,等.大黄素通过内源性线粒体途径和外源性死亡受体途径诱导人宫颈癌He La细胞凋亡的研究[J].中国中医药科技,2013,20(1):37.
[97] Xu Y,Ge R,Du J,et al. Corosolic acid induces apoptosisthrough mitochondrial pathway and caspase activation in humancervix adenocarcinoma He La cells[J]. Cancer Lett,2009,284(2):229.
[98] Kozma S C,Thomas G. Regulation of cell size in growth,devel-opment and human disease:PI3K,PKB and S6K[J]. Bioessays,2002,24(1):65.
[99] Brazil D P,Yang Z Z,Hemmings B A. Advances in protein ki-nase B signalling:AKTion on multiple fronts[J]. Trends BiochemSci,2004,29(5):233.
[100] Arboleda M J,Lyons J F,Kabbinavar F F,et al. Overexpressionof AKT2/protein kinase B beta leads to up-regulation of beta1 in-tegrins,increased invasion,and metastasis of human breast andovarian cancer cells[J]. Cancer Res,2003,63(1):196.
[101] Bai C,Yang X,Zou K,et al. Anti-proliferative effect of RCE-4from Reineckia carnea on human cervical cancer He La cells by in-hibiting the PI3K/Akt/m TOR signaling pathway and NF-κB acti-vation[J]. N-S Arch Pharmacol,2016,389(6):573.
[102] Karin M,Benneriah Y. Phosphorylation meets ubiquitination:thecontrol of NF-[kappa]B activity[J]. Annu Rev Immunol,2000,18(1):621.
[103]甘自立,朱瑞杰,朱会珍,等. NF-κB信号通路在宫颈癌中的研究进展[J].实验与检验医学,2014(3):272.
[104] Zeng L,Zhen Y,Chen Y,et al. Naringin inhibits growth and in-duces apoptosis by a mechanism dependent on reduced activationof NFκB/COX2caspase-1 pathway in He La cervical cancer cells[J]. Int J Oncol,2014,45(5):1929.
[105] Doorbar J,Quint W,Banks L,et al. The Biology and life-cycleof human papillomaviruses[J]. Vaccine,2012,30(5):55.
[106]张燕茹,王月云.宫颈癌防治研究进展[J].中国肿瘤,2015,24(12):998.
[107] Matsubara S,Takeda K,Kodama T,et al. IL-2 and IL-18 atten-uation of airway hyperresponsiveness requires STAT4,IFN-gam-ma,and natural killer cells[J]. Am J Respir Cell Mol Biol,2007,36(3):324.
[108] Gangwar R,Pandey S,Mittal R D,et al. Association of interfer-on-y+874A polymorphism with the risk of developing cervicalcancer in north-Indian population[J]. BJOG,2009,116(12):1671.
[109]任永吉,李冬雷.苦参碱注射液对宫颈癌患者化疗增敏作用及对患者生存质量和免疫功能的影响[J].现代中西医结合杂志,2017,26(23):2535.
[110]卫东锋.红芪多糖调节免疫及抗肿瘤作用的蛋白质组学研究[D].兰州:兰州大学,2012.
[111]李健.龙葵多糖亚级分1a抗宫颈癌及免疫调节作用研究[D].秦皇岛:燕山大学,2009.
[112]孔赛,韩凤娟,张志刚.中药抗宫颈癌HPV感染的研究进展[J].世界中西医结合杂志,2014,9(3):319.
[2]于浩,杜建玲.穿山龙皂苷的药理作用及机制的研究现状[J].中国中药杂志,2017,42(24):4694.
[3]程丽艳,屠凌岚,史红.p38MAPK对慢性前列腺炎疼痛的影响及槲皮素的干预作用[J].中国现代应用药学,2016,33(8):984.
[4]陈娜,杨滨.西红花非药用部位化学成分和药理作用研究进展[J].中国中药杂志,2018,43(14):2884.
[5]尤良震,林逸轩,方朝晖,等.黄芪甲苷治疗糖尿病及其并发症药理作用研究进展[J].中国中药杂志,2017,42(24):4700.
[6]万英洁,夏建新,唐丽.新疆一枝蒿化学成分、药理作用及临床应用研究进展[J].中国中药杂志,2017,42(23):4565.
[7]陈影,陈两绵,仝燕,等.山豆根药理毒理研究进展[J].中国中药杂志,2017,42(13):2439.
[8]张旻昱,吴宏伟,许利平,等.五味子及其活性成分治疗心脑血管疾病药理作用的研究进展[J].中国中药杂志,2018,43(8):1536.
[9]曾婧,王芳.中药及其单体治疗HPV感染宫颈癌的研究进展[J].西北药学杂志,2015,30(3):318.
[10]何秀霞,张春兰,何乃彦,等.独角莲提取液体外抗宫颈癌He La细胞增殖和诱导凋亡的研究[J].时珍国医国药,2011,22(7):1620.
[11]李鑫,于波,张素霜,等.甘草提取物(GC-X)体外诱导人宫颈癌He La细胞凋亡作用的研究[J].黑龙江畜牧兽医,2016(6):198.
[12]王晓华,尹元琴,马萍,等.骆驼蓬全草提取物的抗肿瘤作用[J].沈阳药科大学学报,2006,23(8):534.
[13]赵相轩.水龙骨提取物对宫颈癌He La细胞增殖和凋亡的影响[J].临床肿瘤学杂志,2018,23(2):122.
[14]贺海波,白彩虹,石孟琼,等.威灵仙不同部位对人宫颈癌CaSKi细胞增殖抑制作用实验研究[C].北京:2012全国临床中药学学术研讨会,2012.
[15]范鹏莺.夏枯草提取物对人乳头瘤病毒阳性宫颈癌细胞的凋亡作用[J].药物评价研究,2016,39(3):388.
[16]李桂玲,归绥琪,王莉,等.掌叶半夏有效提取物对He La细胞的作用及机制[J].中国中西医结合杂志,2010,30(3):303.
[17]葛文静,段冷昕,刘玲,等.壁虎醇提物抑制人宫颈癌SiHa细胞迁移及侵袭的研究[J].中国临床药理学杂志,2016,32(10):913.
[18]周永芹,韩莉.蜈蚣提取物对宫颈癌Caski细胞增殖的抑制效应[J].中国组织工程研究,2007,11(34):6805.
[19]杨培民,代龙,李钦青,等.白花蛇舌草多糖对人宫颈癌He La细胞和人肝癌Bel-7402细胞生长的影响[J].现代中药研究与实践,2010(3):32.
[20]靳祎,肖锋,武均宜,等.刺五加多糖下调Survivin蛋白表达诱导He La细胞凋亡[J].中成药,2016,38(4):902.
[21] Cao W,Li X Q,Wang X,et al. A novel polysaccharide,isolatedfrom Angelica sinensis(Oliv.)diels induces the apoptosis of cervi-cal cancer He La cells through an intrinsic apoptotic pathway[J].Phytomedicine,2010,17(8/9):598.
[22]杨婧,戚基萍,王锐,等.红花多糖对人宫颈癌He La细胞增殖和VEGF表达的影响[J].中国实验方剂学杂志,2016(8):111.
[23]姜恩平,王卓,陈建光,等. ERK信号途径介导五味子多糖对He La细胞凋亡和侵袭的作用[J].时珍国医国药,2015(8):1892.
[24]杨滨,娄晓明,吴春丽,等.银杏外种皮多糖对人宫颈癌细胞系Siha增殖及侵袭的影响[J].实用药物与临床,2011,14(3):179.
[25]周聪,孙月,李德海,等.柳蘑多糖对肿瘤细胞增殖抑制作用的研究[J].现代食品科技,2017,33(9):56.
[26]魏士杰,陈文强.云芝子实体多糖对人宫颈癌He La细胞生长和凋亡的影响研究[J].四川大学学报:自然科学版,2016,53(5):1162.
[27] Jose G M,Kurup G M. Sulfated polysaccharides from Padina tet-rastromatica arrest cell cycle,prevent metastasis and downregulateangiogenic mediators in He La cells[J]. Bioactive Carbohydrates&Dietary Fibre,2017,12:7.
[28]贾艳菊,代玲,张灿.龙葵生物碱诱导He La细胞凋亡的研究[J].动物医学进展,2010,31(8):51.
[29]张培,王海琳,张恒亮,等.苦参碱对宫颈癌SiHa细胞增殖的抑制作用及JAK-STAT信号通路的影响[J].现代肿瘤医学,2014,22(8):1790.
[30]狄晓鸿,高英敏,郭红云.黄连素对人宫颈癌He La细胞株的体外作用研究[J].中国中医药信息杂志,2008,15(1):30.
[31]王远兴,贾素花,曾雯瑜,等.卵叶娃儿藤生物碱对宫颈癌细胞株He La的体外作用[J].食品科学,2008,29(11):609.
[32]刘诗伶.去氢骆驼蓬碱对宫颈癌的抑制作用及其分子机制研究[D].南昌:南昌大学,2018.
[33]张莹,张起辉,吴立军,等.吴茱萸碱诱导人宫颈癌He La细胞凋亡过程中非caspase调控因素[J].中国药理学通报,2004,20(1):61.
[34]周斌,于世英.羟基喜树碱对宫颈癌He La细胞的放射增益作用及影响因素的研究[J].华中科技大学学报:医学版,2006,35(3):396.
[35]张如松,叶益萍.白首乌甾体总苷的体外抗肿瘤作用[J].中草药,2000,31(8):599.
[36]刘志华,王刚,沈建飞.柴胡皂苷-D抑制宫颈癌He La细胞的分子机制研究[J].中华中医药学刊,2016,34(12):2931.
[37]李文,旷雨,孟立峰,等.黄芪甲苷对宫颈癌He La细胞增殖、迁移侵袭作用机制研究[J].中药药理与临床,2018,34(3):39.
[38]高苗,刘娟娟,王栋.绞股蓝总皂苷对宫颈癌He La细胞的生长抑制作用及可能的分子机制[J].肿瘤,2013,33(10):868.
[39]熊明华.人参皂苷Rg3对人宫颈癌He La细胞凋亡及Bcl-2/bax基因mRNA表达的影响[J].中国现代医学杂志,2012,22(3):34.
[40]程卉,苏婧婧,候会洁,等.重楼皂苷Ⅰ抗宫颈癌He La细胞作用及机制研究[J].中药材,2013,36(11):1815.
[41]张文秀.薯蓣皂苷元对人宫颈癌细胞增殖的影响[J].中国现代医生,2011,49(26):5.
[42]徐敏,卜平,李瑶瑶.半枝莲黄酮类化合物对体外肿瘤血管生成的影响[J].世界华人消化杂志,2007,15(20):2215.
[43]吾热娅提古丽·克维尔,艾百拉·热合曼,胡尼其古丽·阿巴克,等.蜂胶黄酮短叶松素-3-乙酸酯对人宫颈癌SiHa和大肠癌HT29细胞增殖及凋亡的影响[J].中国新药杂志,2016,25(24):2881.
[44]胡艳玲,李国利,林中翔.葛根素对人宫颈癌He La细胞体外增殖的影响及机制研究[J].中国地方病防治杂志,2017,32(12):1427.
[45]惠双.黄芩苷对宫颈癌细胞株He La的放射增敏作用[J].中国病理生理杂志,2015,31(12):2126.
[46]陈淑梅.高良姜素诱导人乳头瘤病毒阳性的宫颈癌细胞凋亡实验研究[J].中草药,2017,48(5):941.
[47] Wang Hong,Chen Gu,Guo Xinbo,et al.Influence of the stage ofripeness on the phytochemical profiles,antioxidant andantiprolif-erative activities in different parts of Citrus reticulata Blanco cv.Chachiensis[J]. Lwt-Food Sci Te,2016,69:67.
[48]刘心平,徐文弟.银杏叶黄酮提取工艺及对He La细胞Bcl-2mRNA表达的影响[J].哈尔滨医科大学学报,2005,39(3):250.
[49]孙杰,王芍,郭斌,等.三棱黄酮抗He La宫颈癌:降低分裂期细胞比率诱导细胞凋亡[J].食品科学,2011,32(1):210.
[50]崔侨,田代真一,小野寺敏,等.冬凌草甲素通过诱导人宫颈癌He La细胞自噬下调凋亡的机制[J].药学学报,2007,42(1):35.
[51]程齐来,喻亚飞,李映辰,等.藤梨根中乌苏烷三萜化合物A对宫颈癌He La细胞增殖的影响[J].中国实验方剂学杂志,2015,21(24):84.
[52]刘发英,邹阳,杨必成,等.莪术醇对人宫颈癌SiHa和HCC94细胞增殖、自噬及凋亡的影响[J].中药药理与临床,2018,34(1):62.
[53]张巍,秦迎新,李妍,等.胡桃醌诱导宫颈癌Caski细胞凋亡作用[J].中国公共卫生,2014,30(10):1279.
[54]张巍,吴亚猛,陈思瑶,等.胡桃醌对宫颈癌Si Ha细胞增殖及细胞周期的影响[J].吉林大学学报:医学版,2015,41(4):697.
[55]郝臻凤,刘静,张瑜,等.紫草素对宫颈癌He La细胞增殖、侵袭和迁移的影响[J].中国实验方剂学杂志,2015,21(6):91.
[56]张雪青,邵邻相,吴文才,等.白术挥发油抑菌及抗肿瘤作用研究[J].浙江师范大学学报:自然科学版,2016,39(4):436.
[57]邹辉,杨郴,易美玲,等.白术化学成分分离鉴定[J].中国实验方剂学杂志,2016,22(17):43.
[58] Wang J,Lu J,Lv C,et al. Three new triterpenoid saponins fromroot of Gardenia jasminoides Ellis[J]. Fitoterapia,2012,83(8):1396.
[59]韩苏夏,朱青,杜蓓茹,等.薏苡仁酯诱导人宫颈癌He La细胞凋亡的实验研究[J].肿瘤,2002,22(6):481.
[60]戴彦迪,王玉姝,周晓棉,等.蟾酥脂质体注射液的抗肿瘤作用[J].沈阳药科大学学报,2007,24(9):568.
[61]赵俊云,杨晓敏,郭健.丹皮酚抑制SiHa细胞增殖及COX-2转录的实验研究[J].中医药学报,2016,44(1):52.
[62]夏明钰,王敏伟,田代真一,等.厚朴酚通过改变Bax/Bcl-XL表达和激活caspase诱导人宫颈癌He La细胞凋亡[J].中国药理学通报,2005,21(3):318.
[63]邹姝姝,肖琴,李亚妹,等.苏木总酚对宫颈癌细胞的作用[J].重庆理工大学学报:自然科学,2010,24(3):33.
[64]潘纪红,王海滨,杜晓飞,等.虎杖苷通过P13K/AKT/m TOR信号通路诱导人宫颈癌细胞凋亡的初步研究[J].中国中药杂志,2017,42(12):2345.
[65] Yu J,Qian H,Li Y,et al. Arsenic trioxide(As2O3)reduces theinvasive and metastatic properties of cervical cancer cells in vitroand in vivo[J]. Gynecol Oncol,2007,106(2):400.
[66]林晨,拉莱·苏祖克,史永华,等.三氧化二砷对裸鼠宫颈癌移植瘤的作用及机制[J].肿瘤防治研究,2011,38(4):369.
[67]尹伶,濮德敏,韦立蓓,等. As4S4诱导宫颈癌He La细胞凋亡及对端粒酶活性的影响[J].中国现代医学杂志,2008,18(3):298.
[68]谢江碧,贺卫国,翁宁,等.蚯蚓中抗肿瘤蛋白组分的提取分离及其抗肿瘤活性[J].中国生物化学与分子生物学报,2003,19(3):359.
[69]李兴暖,牛力,赵勇.地鳖虫纤溶活性蛋白组分抑制肿瘤作用研究[J].时珍国医国药,2011,22(5):1149.
[70]孔赛,韩凤娟,张志刚.中药抗宫颈癌HPV感染的研究进展[J].世界中西医结合杂志,2014,9(3):319.
[71]李桂玲,夏晴,陈松华,等.掌叶半夏提取物的有效部位对宫颈癌细胞株HPVE6和P53基因表达的影响[J].中华中医药杂志,2012(1):110.
[72] Jiang E,Sun X,Kang H,et al. Dehydrocostus lactone inhibitsproliferation,antiapoptosis,and invasion of cervical cancer cellsthrough PI3K/Akt signaling pathway[J]. Int J Gynecol Cancer,2015,25(7):1179.
[73] Munagala R,Aqil F,Jeyabalan J,et al. TanshinoneⅡAinhibitsviral oncogene expression leading to apoptosis and inhibition ofcervical cancer[J]. Cancer Lett,2015,356(2):536.
[74] Kaufmann S H,Earnshaw W C. Induction of apoptosis by cancerchemotherapy[J]. Exp Cell Res,2000,256(1):42.
[75] Leblanc A C. Natural cellular inhibitors of caspases[J]. ProgNeuropsychopharmacol Biol Psychiatry,2003,27(2):215.
[76]许立,李霞,张茶,等.东北红豆杉中19种单体化合物对宫颈癌He La细胞增殖的影响[J].武警医学,2011,22(6):513.
[77]贾慧敏,张祖珣,张海燕,等.蚯蚓组织中抑制肿瘤细胞生长物质的分离提取及其作用机制初探[J].肿瘤,2003,23(6):481.
[78] Lipfert L,Haimovich B,Schaller M D,et al. Integrin-dependentphosphorylation and activation of the protein tyrosine kinasepp125FAK in platelets.[J]. J Cell Bio,1992,119(4):905.
[79] Sulzmaier F J,Jean C,Schlaepfer D D. FAK in cancer:mecha-nistic findings and clinical applications[J]. Nat Rev Cancer,2014,14(9):598.
[80] Hsueh C,Lin J D,Wu I C,et al. Vascular endothelial growthfactors and angiopoietins in presentations and prognosis of papilla-ry thyroid carcinoma[J]. J Surg Oncol,2011,103(5):395.
[81] Park J H,Park K J,Kim Y S,et al. Serum angiopoietin-2 as aclinical marker for lung cancer[J]. Chest,2007,132(1):200.
[82] Yalcin M,Dyskin E,Lansing L,et al. Tetraiodothyroacetic acid(tetrac)and nanoparticulate tetrac arrest growth of medullary car-cinoma of the thyroid.[J]. J Clin Endocr Metab,2010,95(4):1972.
[83] Wray C J,Rilo H L,Ahmad S A. Colon cancer angiogenesis andantiangiogenic therapy[J]. Expert Opin Inv Drug,2004,13(6):631.
[84]王立岩,许晓艳,盛敏佳,等. HIF-1α及VEGF在宫颈癌组织中的表达及其临床意义[J].中国实验诊断学,2009,13(12):1749.
[85]周吉华,张庆华.灵芝孢子对老年宫颈癌患者外周血T淋巴细胞亚群及VEGF的影响[J].中国妇幼保健,2014,29(13):2021.
[86]余杰,杨振国,陈美珍,等.牡蛎活性肽体外诱导He La细胞凋亡及其作用机制[J].食品科学,2012,33(21):290.
[87] Shay J W,Wright W E. Role of telomeres and telomerase in canc-er[J].Eur J Cancer,2011,21(6):349.
[88] Günes C,Rudolph K L. The role of telomeres in stem cells andcancer.[J]. Cell,2013,152(3):390.
[89]刘晶,周天兴,刘蕊,等.大黄素对宫颈癌He La细胞端粒损伤作用的研究[J].中国细胞生物学学报,2018,40(2):178.
[90] Nüssleinvolhard C,Wieschaus E. Mutations affecting segmentnumber and polarity in drosophila[J]. Nature, 1980, 287(5785):795.
[91] Krieghoff E,Behrens J,Mayr B. Nucleo-cytoplasmic distributionof beta-catenin is regulated by retention[J]. J Cell Sci,2006,119(7):1453.
[92] Green D R,Reed J C. Mitochondria and apoptosis[J]. Science,1998,281(5381):1309.
[93] Tan K O,Fu N S,Chan S L,et al. MAP1 is a mitochondrial ef-fector of Bax[J]. Proc Natl Acad Sci USA,2005,102(41):14623.
[94] Garrido C,Galluzzi L,Brunet M,et al. Mechanisms of cyto-chrome c release from mitochondria[J]. Cell Death Differ,2006,13(9):1423.
[95] Hengartner M O. The biochemistry of apoptosis[J]. Nature,2000,407(6805):770.
[96]王耀先,郝慧南,陈秀玮,等.大黄素通过内源性线粒体途径和外源性死亡受体途径诱导人宫颈癌He La细胞凋亡的研究[J].中国中医药科技,2013,20(1):37.
[97] Xu Y,Ge R,Du J,et al. Corosolic acid induces apoptosisthrough mitochondrial pathway and caspase activation in humancervix adenocarcinoma He La cells[J]. Cancer Lett,2009,284(2):229.
[98] Kozma S C,Thomas G. Regulation of cell size in growth,devel-opment and human disease:PI3K,PKB and S6K[J]. Bioessays,2002,24(1):65.
[99] Brazil D P,Yang Z Z,Hemmings B A. Advances in protein ki-nase B signalling:AKTion on multiple fronts[J]. Trends BiochemSci,2004,29(5):233.
[100] Arboleda M J,Lyons J F,Kabbinavar F F,et al. Overexpressionof AKT2/protein kinase B beta leads to up-regulation of beta1 in-tegrins,increased invasion,and metastasis of human breast andovarian cancer cells[J]. Cancer Res,2003,63(1):196.
[101] Bai C,Yang X,Zou K,et al. Anti-proliferative effect of RCE-4from Reineckia carnea on human cervical cancer He La cells by in-hibiting the PI3K/Akt/m TOR signaling pathway and NF-κB acti-vation[J]. N-S Arch Pharmacol,2016,389(6):573.
[102] Karin M,Benneriah Y. Phosphorylation meets ubiquitination:thecontrol of NF-[kappa]B activity[J]. Annu Rev Immunol,2000,18(1):621.
[103]甘自立,朱瑞杰,朱会珍,等. NF-κB信号通路在宫颈癌中的研究进展[J].实验与检验医学,2014(3):272.
[104] Zeng L,Zhen Y,Chen Y,et al. Naringin inhibits growth and in-duces apoptosis by a mechanism dependent on reduced activationof NFκB/COX2caspase-1 pathway in He La cervical cancer cells[J]. Int J Oncol,2014,45(5):1929.
[105] Doorbar J,Quint W,Banks L,et al. The Biology and life-cycleof human papillomaviruses[J]. Vaccine,2012,30(5):55.
[106]张燕茹,王月云.宫颈癌防治研究进展[J].中国肿瘤,2015,24(12):998.
[107] Matsubara S,Takeda K,Kodama T,et al. IL-2 and IL-18 atten-uation of airway hyperresponsiveness requires STAT4,IFN-gam-ma,and natural killer cells[J]. Am J Respir Cell Mol Biol,2007,36(3):324.
[108] Gangwar R,Pandey S,Mittal R D,et al. Association of interfer-on-y+874A polymorphism with the risk of developing cervicalcancer in north-Indian population[J]. BJOG,2009,116(12):1671.
[109]任永吉,李冬雷.苦参碱注射液对宫颈癌患者化疗增敏作用及对患者生存质量和免疫功能的影响[J].现代中西医结合杂志,2017,26(23):2535.
[110]卫东锋.红芪多糖调节免疫及抗肿瘤作用的蛋白质组学研究[D].兰州:兰州大学,2012.
[111]李健.龙葵多糖亚级分1a抗宫颈癌及免疫调节作用研究[D].秦皇岛:燕山大学,2009.
[112]孔赛,韩凤娟,张志刚.中药抗宫颈癌HPV感染的研究进展[J].世界中西医结合杂志,2014,9(3):319.