天然活性化合物奥科呋喃纳米脂质体抗肿瘤作用研究
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摘要
目的研究天然活性化合物奥科呋喃[C18H17NO6,6-乙酰基-2-(1-氨基-亚乙基)-7,9-二羟基-8,9b-二甲基-9b H-二苯呋喃-1,3-二酮]纳米脂质体的体外和体内抗肿瘤作用。方法采用薄膜分散-超声法制备纳米脂质体,采用HPLC法测定纳米脂质体载药量。体外培养人肝癌Hep G2细胞、人结肠癌HCT-116细胞、云南宣威肺癌XWLC-05细胞,采用MTT法评价纳米脂质体体外抗癌作用。制备HCT-116裸鼠移植瘤模型,观察载药纳米脂质体体内对裸鼠移植肿瘤的生长抑制作用。结果载药纳米脂质体的载药量为1.26 mg/m L。载药纳米脂质体对XWLC-05、HCT-116、Hep G2细胞的半数抑制浓度(IC50)分别为2.48、0.86、1.86μg/m L,且在4μg/m L时对XWLC-05、HCT-116、Hep G2细胞的增殖抑制率分别为85.59%、99.95%、96.91%(P<0.01)。裸鼠肿瘤相对增殖率最小为50.98%,具有体内抗肿瘤作用。结论天然活性化合物奥科呋喃可制备为纳米脂质体;体外细胞实验表明,奥科呋喃纳米脂质体对癌细胞作用呈明显的剂量-效应关系;裸鼠体内实验发现,载药纳米脂质体对裸鼠移植瘤的生长有抑制作用。
Objective To study the antitumor effect of natural active compound usenamine(C18 H17 NO6, 6-acety1-2-(1-amino-ethylidene)-7,9-dihydroxy-8,9 b-dimethy1-9 b H-dibenzofuran-1,3-dione) nano-liposomes in vitro and in vivo. MethodsNano-liposomes were prepared by thin film dispersion-ultrasonic method. The drug loading of nano-liposomes was determined by HPLC. The cancer cells were cultured in vitro, and the absorbance values were measured by MTT method to evaluate the anticancer effect in vitro. A nude mouse xenograft model was established to observe the growth inhibitory effect of drug-loaded nano-liposomes on tumor growth in nude mice. Results The drug loading of drug-loaded nano-liposomes was 1.26 mg/m L. The IC50 of the drug-loaded nano-liposomes in the XWLC-05, HCT-116, and Hep G2 cells were 2.48 μg/m L, 0.86 μg/m L, and 1.86 μg/m L, respectively, and the inhibition rates of XWLC-05, HCT-116, and Hep G2 cells administered at a dose of 4 μg/m L were 85.59%, 99.95%, and 96.91%, respectively(P < 0.01). The minimum relative tumor proliferation rate of nude mice was 50.98%, and usenamine nano-liposomes had antitumor effect in vivo. Conclusion The natural active compound usenamine can be prepared as a nano-liposome. In vitro cell experiments showed that usenamine nano-liposomes had a dose-effect relationship with cancer cells. In vivo experiments in nude mice found that drug-loaded nano-liposomes had inhibitory effect on tumors.
Objective To study the antitumor effect of natural active compound usenamine(C18 H17 NO6, 6-acety1-2-(1-amino-ethylidene)-7,9-dihydroxy-8,9 b-dimethy1-9 b H-dibenzofuran-1,3-dione) nano-liposomes in vitro and in vivo. MethodsNano-liposomes were prepared by thin film dispersion-ultrasonic method. The drug loading of nano-liposomes was determined by HPLC. The cancer cells were cultured in vitro, and the absorbance values were measured by MTT method to evaluate the anticancer effect in vitro. A nude mouse xenograft model was established to observe the growth inhibitory effect of drug-loaded nano-liposomes on tumor growth in nude mice. Results The drug loading of drug-loaded nano-liposomes was 1.26 mg/m L. The IC50 of the drug-loaded nano-liposomes in the XWLC-05, HCT-116, and Hep G2 cells were 2.48 μg/m L, 0.86 μg/m L, and 1.86 μg/m L, respectively, and the inhibition rates of XWLC-05, HCT-116, and Hep G2 cells administered at a dose of 4 μg/m L were 85.59%, 99.95%, and 96.91%, respectively(P < 0.01). The minimum relative tumor proliferation rate of nude mice was 50.98%, and usenamine nano-liposomes had antitumor effect in vivo. Conclusion The natural active compound usenamine can be prepared as a nano-liposome. In vitro cell experiments showed that usenamine nano-liposomes had a dose-effect relationship with cancer cells. In vivo experiments in nude mice found that drug-loaded nano-liposomes had inhibitory effect on tumors.
引文
[1]陈万青,李贺.人群肿瘤监测在癌症防控中的作用[J].肿瘤预防与治疗,2018,31(1):1-4.
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[15]Torchilin V P.Recent advances with liposomes as pharmaceutical carriers[J].Nat Rev Drug Discov,2005,4(2):145-160.
[16]张文娟,陈一桢,唐兰如,等.二氢杨梅素长循环纳米脂质体的制备及大鼠体内药动学研究[J].中草药,2018,49(4):806-813.
[17]罗小燕,吕竹芬,陈燕忠,等.薄膜-超声法制备芦丁固体脂质纳米粒的研究[J].西北药学杂志,2015,30(3):267-270.
[18]高惠静,安惠霞,陈蓓,等.与纳米脂质体制备方法相关的中国发明专利[J].中国药房,2016,27(7):976-977.
[19]郭倩倩.紫杉醇纳米脂质体的研究进展[J].中国药科大学学报,2014,45(5):599-606.
[20]Wang S J,Hou W,Sun K,et al.Effects of several auxiliary materials on the particle size and Zeta potential of paclitaxel liposome[J].Med Plant,2011,2(10):52-55.
[21]龚连生,曾雅娟,张阳德,等.阿霉素纳米脂质体的生物学效应研究[J].中国现代医学杂志,2009,19(24):3760-3762.
[2]Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,doi:10.3322/caac.21492.
[3]Cai Y,Xue M,Chen W,et al.Expenditure of hospital care on cancer in China,from 2011 to 2015[J].Chin J CancerRes,2017,29(3):253-262.
[4]胡建平,饶克勤,钱军程,等.中国慢性非传染性疾病经济负担研究[J].中国慢性病预防与控制,2007,15(3):189.
[5]Gai R Y,Xu H L,Qu X J,et al.Dynamic of modernizing traditional Chinese medicine and the standards system for its development[J].Drug Discov Ther,2008,2(1):2-4.
[6]H X Q,Duan J L,Zhou J,et al.Effects of two traditional Chinese cooking oils,canola and pork,on p H and cholic acid content of faeces and colon tumorigenesis in kunming mice[J].Asian Pacific J Cancer Prevent,2015,16(15):6225-6229.
[7]税靖霖,贺小琼,姜重阳,等.赤星衣酸甲酯的抗癌作用及机制研究[J].中草药,2017,48(12):2474-2480.
[8]He X Q,Hu Y,Winter J,et al.Anti-mutagenic lichen extract has double-edged effect on azoxymethane-induced colorectal oncogenesis in C57BL/6J mice[J].ToxicolMech Methods,2010,20(1):31-35.
[9]He X Q.The inhibitory effects of natural plant extract AMH on the mutagenicity of several carcinogens in vitro[J].Chin J Lymphol Oncol,2004,3(2):105-107.
[10]贺小琼.天然植物制剂AMH体外抑制多种强致癌物的致突变作用[J].肿瘤,2003,23(6):494-496.
[11]贺小琼,李凝诗,李凤,等.真菌提取物AMH的肿瘤化学预防活性组分追踪[J].癌变·畸变·突变,2011,23(3):166-170.
[12]贺小琼.二羟二苯并[b,f][1,5]二氧杂辛环类化合物制备方法及其药用组合物和应用:中国,201811420247.3[P].2018-11-27.
[13]李可欣,常莎莎,邸东华,等.配体介导的纳米脂质体作为肿瘤疫苗载体的可行性评价[J].沈阳药科大学学报,2017,34(1):23-27.
[14]Tardi P,Choice E,Masin D,et al.Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models[J].Cancer Res,2000,60(13):3389-3393.
[15]Torchilin V P.Recent advances with liposomes as pharmaceutical carriers[J].Nat Rev Drug Discov,2005,4(2):145-160.
[16]张文娟,陈一桢,唐兰如,等.二氢杨梅素长循环纳米脂质体的制备及大鼠体内药动学研究[J].中草药,2018,49(4):806-813.
[17]罗小燕,吕竹芬,陈燕忠,等.薄膜-超声法制备芦丁固体脂质纳米粒的研究[J].西北药学杂志,2015,30(3):267-270.
[18]高惠静,安惠霞,陈蓓,等.与纳米脂质体制备方法相关的中国发明专利[J].中国药房,2016,27(7):976-977.
[19]郭倩倩.紫杉醇纳米脂质体的研究进展[J].中国药科大学学报,2014,45(5):599-606.
[20]Wang S J,Hou W,Sun K,et al.Effects of several auxiliary materials on the particle size and Zeta potential of paclitaxel liposome[J].Med Plant,2011,2(10):52-55.
[21]龚连生,曾雅娟,张阳德,等.阿霉素纳米脂质体的生物学效应研究[J].中国现代医学杂志,2009,19(24):3760-3762.