β-榄香烯逆转胃癌细胞株阿霉素耐药性的作用及机制研究

摘要

Objective To explore the effect of p-elemene on the reverse of multi-drug resistance and the expressions of the poly ADP-ribose polymerase protein (PARP) and P-glycoprotein (P-gp) in SGC7901/Adr cells. Methods MTT method was used to detect the sensitivity of cell and its reverse of multi-drug resistance. Intracellular accumulation of adriamycin in SGC7901/Adr cells was observed by fluores-cent-spectrophotometry. Cell apoptosis was determined by flow cytometry after propidium iodide staining. Expressions of proteins were detected by Western blot. All experimental data were dealt with by SPSS (13.0 soft). Results The inhibitory effect of P-elemene on both SGC7901 and SGC7901/Adr was detected in a dose-dependent manner. Low-cytotoxic dose of P-elemene could obviously decrease the IC50 value of SGC7901/Adr cells to adriamycin (P < 0.05). The reversing fold was 1.41. Low-cytotoxic dose of P-elemene could increase the intracellular accumulation of adriamycin evidently and remarkably induce the activated fragment of PARP and decrease the P-gp expression in SGC7901/ Adr cells. Conclusion P-elemene could partially reverse the multi-drug resistance to adriamycin in SGC7901/Adr cells,which is related to the increased accumulation of intracellular adriamycin,the activated fragment of PARP and the decreased expression of P-gp.%目的 探讨β-榄香烯对多药耐药胃癌细胞SGC7901/Adr的耐药逆转及其对聚腺苷二磷酸聚合酶(PARP)和P-糖蛋白(P-gp)表达的影响.方法 采用MTT法检测细胞的药物敏感性及耐药逆转,流式细胞术检测细胞内药物累积,流式细胞术PI染色检测细胞凋亡,Western blot检测蛋白表达.结果 β-榄香烯对胃癌SGC7901及SGC7901/Adr细胞均具有增殖抑制作用,且具有量效关系.阿霉素与低毒剂量β-榄香烯共同作用SGC7901/Adr细胞,其IC50显著降低(P＜0.05),耐药逆转倍数为1.41.与阿霉素单药组相比,加入低毒剂量β-榄香烯后,细胞内阿霉素的蓄积浓度明显增加,差异有统计学意义(P＜0.05).β-榄香烯作用后诱导PARP裂解,同时下调了P-gp蛋白表达.结论 β-榄香烯部分逆转SGC7901/Adr细胞对阿霉素的耐药性,其机制与增加细胞内阿霉素的蓄积,诱导PARP裂解及降低P-gp的表达有关.