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

Reversal of Resistance to Adriamycin in Human Gastric Cancer by β-elemene

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。

Objective To explore the effect of β-elemene on the reverse of multi-drug resistance and the expressions of the poly ADP-ribose polymerase protein （PARP） and P-glyeopmtein （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 fluorescent-spectropbotometry. 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 [3-elemene on both SGC7901 and SGC7901/Adr was detected in a dose-dependent manner. Low-cytotoxic dose of β-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 β-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 [3-elemene could partially reverse the multi-drug resistance to adriamycin in SGC7901/Adr cells,which is related to the increased accumulation of intraeellular adriamycin, the activated fragment of PARP and the decreased expression of P-gp.