丹参逆转胃癌耐药细胞的作用及其机制分析

Effect and related mechanism of Salvia miltiorrhiza on human drug-resistant gastric cancar cell

目的探讨丹参对人胃癌耐药细胞系SGC7901/ADR耐药性的逆转作用及其机制。方法以不同浓度的丹参(SAL)处理耐药系SGC7901/ADR及敏感系SGC7901细胞,四甲基偶氮唑盐(MTT)比色法检测丹参对两种细胞系的毒性及半数抑制率(IC50),流式细胞仪(FCM)检测丹参对两种细胞内ADM浓度和细胞周期的影响,SP法免疫组化染色检测两种细胞P-糖蛋白(P-gp)和DNA拓扑异构酶Ⅱ(TopoⅡ)的表达。结果丹参的非细胞毒性药物剂量为500 mg/L以下;丹参可逆转SGC7901/ADR细胞对ADM的耐药性,逆转倍数为1.89(P<0.01);提高细胞内ADM浓度,ADM增加1.55倍(P<0.05);丹参使细胞周期阻滞于G1、G2期;对细胞膜P-gp的表达轻度下降、TopoⅡ的表达略有增加,但无显著性差异(P均>0.05)。结论丹参对SGC7901和SGC7901/ADR细胞无杀伤作用。其机制是丹参能增加耐药细胞内化疗药物浓度,使DNA合成期(S期)细胞含量下降。

Objective It is to approach the effects and related mechanism of Salvia miltiorrhiza（SAL） on reverse the multidrug resistance（MDR） of gastric carcinoma cell line SGC7901/ADR to adriamycin.Methods Drug resistance SGC7901/ADR cells and drug sensitive SGC7901 cells were treated with SAL of several concentrations.The uncytoxicity doses and IC50 of the two cell lines were detected by MTT assay;cell cycle and ADM concentration in the cells were detected by flow cytometry;the expression of P-glycoprotein（P-gp） and topoisomerase Ⅱ （Topo Ⅱ ） in gastric cancer cells were detected by immunohistochemical staining technique. Results The uncytotoxicity doses of SAL was 500 mg/L. IC50 values of ADM of SGC7901/ADR cells were reduced significantly, reversal index （RI） was 1.89 （P 〈 0.01 ）, and ADM concentration in SGC7901/ADR cells was upregulated, upregulated multiple was 1.55 （P 〈 0.05）. SAL made cell cycle blocked in G1, G2 phase. The expression of P-gp in cell membrane reduced slightly and the expression of Topo Ⅱ increased a little, but there was no significant difference （P 〉 0.05）. Conclusion SAL has no effect on SGC7901/ADR and drug sensitive SGC7901 cell line. The reversal mechanism is associated with the increase of the cellular accumulation of antieancerdrug, and decrease of the content of cells which in DNA synthesis phase.