虎杖苷逆转人结肠癌细胞株HT-29奥沙利铂耐药性及机制  

Polydatin reverses the multi-drug resistance to oxaliplatin in human colon HT-29 cells

作　　者：张冬梅[1] 张雅明[1] 

机构地区：[1]上海中医药大学附属曙光医院柏氏肛肠科,上海200000

出　　处：《现代肿瘤医学》2016年第16期2505-2508,共4页Journal of Modern Oncology

基　　金：上海市进一步加快中医药事业发展三年行动计划资助(编号:ZY3-CCCX-1-1008)

摘　　要：目的:探讨虎杖苷对结肠癌耐药细胞株HT-29奥沙利铂(oxaliplatin,OXA)耐药性的逆转作用并探讨其可能的作用机制。方法:采用逐步增加药物浓度的方法建立奥沙利铂耐药结肠癌细胞株HT-29/OXA。MTT和CCK-8法测定虎杖苷对HT-29/OXA细胞的耐药性逆转作用,流式细胞术检测细胞凋亡、周期变化,qRT-PCR检测各组细胞LRP(lung resistance protein)和P-gp(P-glycoprotein)mRNA表达水平,Western blot检测各组细胞LRP和P-gp蛋白的表达水平。结果:虎杖苷使HT-29/OXA细胞对奥沙利铂的敏感性增加,耐药性得到部分逆转(P<0.05)。联合应用对结肠癌耐药细胞株HT-29/OXA生长增殖具有明显抑制作用并且能够通过改变细胞周期引起凋亡(P<0.05)。作用后LRP mRNA和P-gp mRNA表达水平降低,同时下调了LRP和P-gp蛋白表达(P<0.05)。结论:虎杖苷部分逆转HT-29/OXA细胞对奥沙利铂的耐药性,其机制与降低细胞内LRP基因从而导致P-gp的表达降低有关。Objective：To investigate of effect of polydatin on the reversal of multi - drug resistance in HT - 29 /OXA cells and explore its underlying mechanisms. Methods：Oxaliplatin resistant HT - 29 / OXA cells were estab-lished by gradually increase the concentration of oxaliplatin and intermittent treatment with high - dose concentration on parental cells（HT - 29）. MTT and CCK - 8 assay were used to detect cell proliferation,flow cytometry was used to detect apoptosis and cell cycle,quantitative real time PCR（qRT - PCR）and Western blot were used to determine the expression levels of lung resistance protein（LRP）and P - glycoprotein（P - gp）mRNA and protein,respective-ly. Results：Oxaliplatin in combination with polydatin significantly inhibited cell proliferation and induced apoptosis with an increase in cell population of G0 / G1 phase in HT - 29 / OXA cells when compared to oxaliplatin or polydatin used alone（P ﹤ 0. 05）. HT - 29 / OXA cells received oxaliplatin in combination with polydatin treatment also had a lower expression levels of LRP and P - gp mRNA and protein（P ﹤ 0. 05）. Conclusion：Polydatin could partially re-verse the multi - drug resistance to oxaliplatin in HT - 29 / OXA cells,which is related to modulation of LRP and P -gp expression levels.

关 键 词：结肠癌 HT-29 奥沙利铂 多药耐药性 虎杖苷 

分 类 号：R735.35[医药卫生—肿瘤]