竹节参皂苷Ⅳ、Ⅳa和Ⅴ对胃癌SGC-7901细胞增殖、凋亡、迁移及侵袭的作用
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摘要
目的研究竹节参齐墩果烷型皂苷单体对人胃癌SGC-7901细胞的增殖、迁移和侵袭以及凋亡的影响。方法实验分空白对照组、阳性对照组(5-氟脲嘧啶)和竹节参皂苷组。将不同浓度的竹节参皂苷Ⅳ、Ⅳa和Ⅴ分别体外作用于胃癌SGC-7901细胞,采用CCK-8法检测竹节参皂苷对胃癌细胞增殖的抑制能力;利用流式细胞法分析竹节参皂苷对胃癌细胞凋亡的影响;通过划痕实验和Transwell小室检测皂苷对胃癌细胞的迁移能力和侵袭能力的影响。结果作用于细胞48 h后,在37.5～600μg·mL~(-1)的浓度范围内,皂苷Ⅳ、Ⅳa和Ⅴ均以浓度依赖方式抑制胃癌细胞增殖,以皂苷Ⅳa的抑制作用最强;流式细胞法检测显示,250、500μg·mL~(-1)浓度的皂苷Ⅳ、Ⅳa和Ⅴ在作用于胃癌细胞48 h后均表现出不同程度的凋亡诱导作用,且呈浓度依赖性,其中以皂苷Ⅳ的作用最强;250、500μg·mL~(-1)浓度的皂苷Ⅳ、Ⅳa和Ⅴ作用24 h后可明显抑制胃癌细胞的迁移和侵袭,且呈浓度依赖性。结论竹节参齐墩果烷型皂苷能够明显诱导胃癌SGC-7901细胞的凋亡,并可显著抑制胃癌SGC-7901细胞的增殖、迁移和侵袭。
Objective To study the effect of the oleanane-type triterpene saponins of Panax japonicus on the proliferation,migration,invasion and apoptosis of human gastric cancer SGC-7901 cells. Methods The cells were divided into blank control group,positive control group(5-fluorouracil) and chikusetsusaponins groups. Different concentrations of chikusetsusaponin Ⅳ, Ⅳa and Ⅴ were respectively applied to SGC-7901 cells in vitro. The inhibitory effect of chikusetsusaponins on the proliferation of gastric cancer cells was assessed by CCK-8 assay. The apoptosis of gastric cancer cells was analyzed by flow cytometry. The effects of chikusetsusaponin on the migration and invasion of gastric cancer cells were detected by scarification test and transwell migration assays. Results Chikusetsusaponins showed a significant concentration-dependent proliferation inhibition in gastric cancer cells within the range of 37.5 to 600 μg·mL~(-1) after 48 h of treatment,especially the chikusetsusaponin Ⅳa. The flow cytometry results showed that chikusetsusaponins induced apoptosis of gastric cancer cells at different degree at 250μg·mL~(-1) and 500 μg·mL~(-1) after 48 h treatment,especially the chikusetsusaponin Ⅳ. And,chikusetsusaponins can significantly inhibit the migration and invasion of gastric cancer cells at 250 μg·mL~(-1) and 500 μg·mL~(-1) treated for 24 h. Conclusion Oleanane-type triterpene saponins of Panax japonicus could significantly induce apoptosis of gastric cancer SGC-7901 cells and inhibit their proliferation,invasion and migration.
Objective To study the effect of the oleanane-type triterpene saponins of Panax japonicus on the proliferation,migration,invasion and apoptosis of human gastric cancer SGC-7901 cells. Methods The cells were divided into blank control group,positive control group(5-fluorouracil) and chikusetsusaponins groups. Different concentrations of chikusetsusaponin Ⅳ, Ⅳa and Ⅴ were respectively applied to SGC-7901 cells in vitro. The inhibitory effect of chikusetsusaponins on the proliferation of gastric cancer cells was assessed by CCK-8 assay. The apoptosis of gastric cancer cells was analyzed by flow cytometry. The effects of chikusetsusaponin on the migration and invasion of gastric cancer cells were detected by scarification test and transwell migration assays. Results Chikusetsusaponins showed a significant concentration-dependent proliferation inhibition in gastric cancer cells within the range of 37.5 to 600 μg·mL~(-1) after 48 h of treatment,especially the chikusetsusaponin Ⅳa. The flow cytometry results showed that chikusetsusaponins induced apoptosis of gastric cancer cells at different degree at 250μg·mL~(-1) and 500 μg·mL~(-1) after 48 h treatment,especially the chikusetsusaponin Ⅳ. And,chikusetsusaponins can significantly inhibit the migration and invasion of gastric cancer cells at 250 μg·mL~(-1) and 500 μg·mL~(-1) treated for 24 h. Conclusion Oleanane-type triterpene saponins of Panax japonicus could significantly induce apoptosis of gastric cancer SGC-7901 cells and inhibit their proliferation,invasion and migration.
引文
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[19]郑嘉岗,赵爱光,顾缨,等.胃肠安对人胃癌细胞SGC-7901原位移植瘤细胞增殖和凋亡的影响[J].胃肠病学,2006,11(6):336-339
[20]曹礼慧,蔡绍晖,徐俊,等.4种常用中药注射剂临床抗肿瘤有效性的循证药学评价[J].中国药房,2014,25(3):268-272
[21]李娜,高俊岩,刘敏.细胞凋亡和肿瘤的关系研究进展[J].当代医学,2009,15(16):13-14.
[22]吴建勇,赵德璋.流式细胞仪检测细胞凋亡的几种方法的比较[J].重庆医科大学学报,2010,35(9):1386-1389.
[23]ZHU W,TI AN F,LIU L,et al.Chikusetsu(CHI)triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species(ROS)production[J].Biomed Pharmacother,2017,3:50.
[2]国家药典委员会.中国药典[S].北京:中国医药科技出版社,2015:138-139.
[3]XU W Q,CHOI H K,HUANG L F.State of Panax ginseng research:A global analysis[J].Molecules,2017,22(9):1518.
[4]CHOK W T.Botanical characteristics,pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer[J].Acta Pharmacol Sin,2008,29(9):1109-1118.
[5]武秋爽,陈平,张庆文.竹节参化学成分、药理活性及分析方法研究进展[J].亚太传统医药,2016,12(6):46-54.
[6]杨小林,陈平.竹节参总皂苷对高血脂模型小鼠的影响作用[J].中医药学报,2010,38(6):22-24.
[7]陈龙全,刘杰书,黄琼.竹节参的主要药效与作用机制[J].中华中医药杂志,2009,24(2):197-198.
[8]MORITA T,TANAKA O,KOHDA H.Saponin composition of rhizomes of Panax japonicus collected in South Kyushu,Japan,and its significance in oriental traditional medicine[J].Chemical&Pharmaceutical Bulletin,1985,33(33):3852-3858.
[9]袁丁,左锐,张长城.竹节参总皂苷抑制小鼠肿瘤生长的实验研究[J].时珍国医国药,2007,18(2):277-278.
[10]SONG X,WANG W,ZHANG X,et al.Deglucose chikusetsusaponin a isolated from rhizoma panacis majorisinduces apoptosis in human HepG2 hepatoma cells[J].Mol Med Rep,2015,12(4):5494-5500.
[11]左婷婷,郑荣寿,曾红梅,等.中国胃癌流行病学现状[J].中国肿瘤临床,2017,44(1):52-58.
[12]彭亮.胃癌侵袭转移相关功能基因的研究[D].北京:中国协和医科大学,2009.
[13]张亚龙,房念珍,尤嘉琮,等.肿瘤细胞代谢与肿瘤转移相互关系的研究进展[J].中国肺癌杂志,2014,17(11):812-818.
[14]HUBERT S,ABASTADO J P.The early steps of the metastatic process[J].Med Sci(Paris),2014,30(4):378-384.
[15]伊日贵,徐晓艳,李时荣.肿瘤侵袭转移机制研究进展[J].中华实用诊断与治疗杂志,2014,28(10):937-939.
[16]陈修平,唐正海,石哲,等.肿瘤生物学研究热点与抗肿瘤中药研发策略[J].中国中药杂志,2015,40(17):3416-3422.
[17]LEE S G,KWON M,JANG J P,et al.The ginsenoside metabolite compound K inhibits growth,migration and stemness of glioblastoma cells[J].International Journal of Oncology,2017,51(2):414-424
[18]LING C Q,YUE X Q,LING C.Three advantages of using traditional Chinese medicine to prevent and treat tumor[J].Journal of Chinese integrative medicine,2014,12(4):331-335.
[19]郑嘉岗,赵爱光,顾缨,等.胃肠安对人胃癌细胞SGC-7901原位移植瘤细胞增殖和凋亡的影响[J].胃肠病学,2006,11(6):336-339
[20]曹礼慧,蔡绍晖,徐俊,等.4种常用中药注射剂临床抗肿瘤有效性的循证药学评价[J].中国药房,2014,25(3):268-272
[21]李娜,高俊岩,刘敏.细胞凋亡和肿瘤的关系研究进展[J].当代医学,2009,15(16):13-14.
[22]吴建勇,赵德璋.流式细胞仪检测细胞凋亡的几种方法的比较[J].重庆医科大学学报,2010,35(9):1386-1389.
[23]ZHU W,TI AN F,LIU L,et al.Chikusetsu(CHI)triggers mitochondria-regulated apoptosis in human prostate cancer via reactive oxygen species(ROS)production[J].Biomed Pharmacother,2017,3:50.