Department of Clinical Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Chemotherapy. 2011;57(1):62-70. doi: 10.1159/000321484. Epub 2011 Feb 1.
Multidrug resistance (MDR) presents a serious problem in cancer chemotherapy. Our previous studies have shown that the MDR of K562/DOX cells could be reversed by guggulsterone through inhibiting the function and expression of P-glycoprotein. The purpose of this study was to investigate the reversal effect of guggulsterone on MDR in drug-resistant MCF-7 cells and the parental MCF-7 cells.
MTT cytotoxicity assays, flow cytometry, and Western blot analysis were performed to investigate the antiproliferative effects of the combination of anticancer drugs with guggulsterone, to study the reversal of drug resistance and to examine the inhibitory effects on MRP1 expression.
The results showed that co-administration of guggulsterone (10 μM) resulted in a significant increase in chemosensitivity of MCF-7/DOX cells to doxorubicin, compared with doxorubicin treatment alone (p < 0.01). The fold reversal of 10 μM guggulsterone (11.48) was comparable to that of 10 μM verapamil (13.23). Rhodamine123 and doxorubicin accumulation in MCF-7/DOX cells was significantly enhanced after the incubation with guggulsterone (10 μM), compared with untreated MCF-7/DOX cells (p < 0.01). When doxorubicin (10 μM) was combined with guggulsterone (10 μM), the mean apoptotic population of MCF-7/DOX cells was 24.91%. It was increased by 6.15 times, compared with doxorubicin (10 μM) treatment alone. However, guggulsterone had little inhibitory effect on the expression of MRP1 proteins.
Guggulsterone is a novel and potent MDR reversal agent with the potential to be an adjunctive agent for tumor chemotherapy.
多药耐药（MDR）在癌症化疗中是一个严重的问题。我们之前的研究表明，通过抑制 P-糖蛋白的功能和表达，芝麻素可以逆转 K562/DOX 细胞的 MDR。本研究旨在探讨芝麻素对耐药 MCF-7 细胞及其亲本 MCF-7 细胞的 MDR 逆转作用。
采用 MTT 细胞毒性实验、流式细胞术和 Western blot 分析，研究抗癌药物联合芝麻素的抗增殖作用、耐药逆转作用以及对 MRP1 表达的抑制作用。
结果表明，与单独使用多柔比星相比，联合使用 10 μM 芝麻素可显著增加 MCF-7/DOX 细胞对多柔比星的化疗敏感性（p < 0.01）。10 μM 芝麻素的逆转倍数（11.48）与 10 μM 维拉帕米（13.23）相当。与未经处理的 MCF-7/DOX 细胞相比，孵育 10 μM 芝麻素后 MCF-7/DOX 细胞中罗丹明 123 和多柔比星的蓄积明显增加（p < 0.01）。当多柔比星（10 μM）与芝麻素（10 μM）联合使用时，MCF-7/DOX 细胞的平均凋亡群体为 24.91%。与单独使用多柔比星（10 μM）相比，增加了 6.15 倍。然而，芝麻素对 MRP1 蛋白的表达几乎没有抑制作用。
芝麻素是一种新型有效的 MDR 逆转剂，有可能成为肿瘤化疗的辅助药物。
