虎杖苷逆转人结肠癌细胞株HT-29奥沙利铂耐药性及机制

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。

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

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.