大黄素逆转肿瘤细胞多药抗药性的作用

REVERSAL OF MULTIDRUG RESISTANCE BY EMODIN IN CANCER CELLS

目的：研究中药成分大黄素的核苷转运抑制活性和对肿瘤细胞多药抗药性的逆转作用。方法：采用［３Ｈ］胸苷掺入法测定核苷转运抑制作用，采用ＭＴＴ法检测细胞毒作用，采用流式细胞术测定Ｐ糖蛋白的功能和表达。结果：大黄素能抑制小鼠艾氏腹水癌细胞对［３Ｈ］胸苷的跨膜转运，其ＩＣ５０为９９μｍｏｌ·Ｌ－１。大黄素能增强抗癌药物５氟尿嘧啶、丝裂霉素和氨甲蝶呤对人肝癌ＢＥＬ７４０２细胞的细胞毒作用并能部分逆转人乳腺癌细胞ＭＣＦ７／Ａｄｒ对阿霉素的抗药性。大黄素增加罗丹明１２３在ＭＣＦ７／Ａｄｒ细胞中的蓄积并减少其外排，长时间作用降低了Ｐ糖蛋白的表达。结论：大黄素逆转抗药性的作用与抑制核苷转运、降低Ｐ糖蛋白的功能和表达相关。

AIM: In search of antitumor biochemical modulators from traditional Chinese herbal medicines, emodin has been found to be active. The goal of present study is to investigate the effects of emodin on the nucleoside transport and multidrug resistance in cancer cells. METHODS: Nucleoside transport inhibition was determined by thymidine incorporation assay. The cytotoxicity to cancer cells was determined by MTT assay. The pump efflux activity and the expression of P glycoprotein were examined by flow cytometric assay. RESULTS: Emodin was active in the inhibition of nucleoside transport, with an IC 50 value of 9 9 μmol·L -1 . Emodin markedly enhanced the cytotoxicity of 5 FU, MMC and MTX against human hepatoma BEL 7402 cells and partly reversed the multidrug resistance in human breast cancer MCF 7/Adr cells. Emodin inhibited P gp pump efflux activity and reduced the expression of P gp in MCF 7/Adr cells. CONCLUSION: These findings provide a biological basis for the application of emodin as a biochemical modulator to potentiate the effects of antitumor drugs and reverse the multidrug resistance in cancer cells.