Azrak Rami G, Frank Cheryl L, Ghadersohi Ali, Rustum Youcef M
Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Cancer Biol Ther. 2008 Dec;7(12):1901-8. doi: 10.4161/cbt.7.12.6939. Epub 2008 Dec 7.
This study evaluates methylseleninic acid (MSeA) improvement of paclitaxel efficacy against human ovarian cancer (skov3) with regard to survivin expression. MSeA and paclitaxel alone and in concurrent or sequential combination treatments were tested. Cell growth/death was evaluated using SRB, trypan blue, colony formation and ELISA assays. Cells were transfected with survivin shRNA and survivin's expression was measured using RT-PCR and Western blots. Drugs interaction was further evaluated using isobologram analyses. Different treatments with MSeA did not enhance paclitaxel's efficacy in the wild type skov3. Silencing survivin had no effect on MSeA or paclitaxel efficacy when used alone or in concurrent combination. After sequential combination treatment, synergy and significant induction of apoptosis were observed in cells transfected with survivin shRNA. However, antagonism and minimal induction of apoptosis were observed in empty or scramble survivin shRNA transfected cells. In conclusion, these data suggest that synergy between MSeA and paclitaxel in skov3 is associated with silencing survivin expression.
本研究评估了甲基亚硒酸（MSeA）对紫杉醇抗人卵巢癌（skov3）疗效的改善作用，涉及生存素表达情况。对单独使用MSeA和紫杉醇以及同时或序贯联合治疗进行了测试。使用SRB法、台盼蓝染色、集落形成试验和ELISA检测评估细胞生长/死亡情况。用生存素短发夹RNA（shRNA）转染细胞，并通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测生存素的表达。使用等效线图分析进一步评估药物相互作用。不同的MSeA处理并未增强野生型skov3中紫杉醇的疗效。单独使用或同时联合使用时，沉默生存素对MSeA或紫杉醇的疗效均无影响。序贯联合治疗后，在转染了生存素shRNA的细胞中观察到协同作用和显著的凋亡诱导。然而，在转染空载体或乱序生存素shRNA的细胞中观察到拮抗作用和最小程度的凋亡诱导。总之，这些数据表明，在skov3细胞中，MSeA与紫杉醇之间的协同作用与生存素表达的沉默有关。
