Emodin sensitizes paclitaxel-resistant human ovarian cancer cells to paclitaxel-induced apoptosis in vitro
Emodin sensitizes paclitaxel-resistant human ovarian cancer cells to paclitaxel-induced apoptosis in vitro
复制标题
DOI：
10.3892/or_00000394
复制
发表时间：
2009-06-01
期刊：
影响因子：
4.2
通讯作者：
Zhang, Xiaolei
中科院分区：
文献类型：
--
作者：
Li, Juan;Liu, Peishu;Zhang, Xiaolei
卵巢癌是世界上死亡率最高的妇科恶性肿瘤之一，其耐药性的产生是卵巢癌治疗成功的主要障碍。已有报道大黄素可使人肿瘤细胞对化疗药物敏感。本研究探讨大黄素能否克服A2780/taxol细胞的耐药性。用不同浓度的大黄素单独或联合紫杉醇处理细胞，MTT法检测细胞活力，流式细胞仪检测细胞凋亡。采用QRT-PCR和Western blotting检测mRNA和蛋白质的变化。流式细胞术检测P-糖蛋白的功能。结果表明，大黄素在高浓度时单独诱导细胞凋亡，在低浓度时增加紫杉醇诱导的细胞凋亡。A2780/taxol细胞对紫杉醇的敏感性增强，P-gp、XIAP和Survivin表达下调。综上所述，结果表明大黄素通过增加紫杉醇细胞浓度和使耐药细胞对紫杉醇重新敏感来抑制药物耐药卵巢肿瘤生长的双重作用。我们的研究结果表明，一种创新的化疗策略，使用大黄素与紫杉醇联合增加肿瘤细胞的敏感性的可能性。
Ovarian cancer has the highest mortality rate among gynecologic malignancies in the world, and the development of drug resistance is a major impediment toward Successful treatment of the desease. Emodin has been reported to sensitize human tumor cells to chemotherapeutic agents. The present study investigated whether emodin could overcome chemoresistance of A2780/taxol cells. Cells were treated with different concentration of emodin alone or combined with paclitaxel, then the cell viability was measured by MTT and the apoptosis was determined by flow cytometric analysis. The changes of mRNA and protein were examined by QRT-PCR and Western blotting. The function of P-glycoprotein was also determined by flow cytometry. The results showed that emodin induced apoptosis alone at a high concentration and increased paclitaxel-induced apoptosis at a low concentration. It enhanced the sensitivity of A2780/taxol cells to paclitaxel with down-regulation of P-glycoprotein, XIAP and survivin. Taken together, the results demonstrated a dual role for emodin in the inhibition of drug, resistant ovarian tumor growth by increasing paclitaxel cellular concentration and re-sensitizing the resistant cells to paclitaxel. Our results Suggest the possibility of an innovative chemotherapeutic strategy that uses emodin in combination with paclitaxel to increase the sensitivity of tumor cells.