Silencing survivin results in synergy between methylseleninic acid and paclitaxel against skov3 ovarian cancer cells

Silencing survivin results in synergy between methylseleninic acid and paclitaxel against skov3 ovarian cancer cells
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DOI:
10.4161/cbt.7.12.6939
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发表时间:
2008-12-01
影响因子:
3.6
通讯作者:
Rustum, Youcef M.
Rustum, Youcef M.
中科院分区:
医学3区
文献类型:
--
作者:
Azrak, Rami G.;Frank, Cheryl L.;Rustum, Youcef M.

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本研究评估了甲基亚硒酸(MSeA)对紫杉醇治疗人卵巢癌(skov 3)的疗效的改善,并对MSeA和紫杉醇单独治疗以及同时或序贯联合治疗进行了测试。使用SRB、台盼蓝、集落形成和ELISA测定评价细胞生长/死亡。用Survivin shRNA转染细胞,并使用RT-PCR和Western印迹测量Survivin的表达。使用等效线图分析进一步评价药物相互作用。用MSeA的不同处理没有增强紫杉醇在野生型skov 3中的功效。当单独使用或同时联合使用时,沉默生存素对MSeA或紫杉醇的疗效没有影响。序贯联合处理后,在转染Survivin shRNA的细胞中观察到协同作用和显著诱导凋亡。然而,在空的或杂乱的生存素shRNA转染细胞中观察到拮抗作用和最小的凋亡诱导。总之,这些数据表明,MSeA和紫杉醇在skov 3中的协同作用与沉默生存素表达有关。
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.