Enhanced inhibition of bladder cancer cell growth by simultaneous knockdown of antiapoptotic Bcl-xL and survivin in combination with chemotherapy.
Enhanced inhibition of bladder cancer cell growth by simultaneous knockdown of antiapoptotic Bcl-xL and survivin in combination with chemotherapy.
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DOI：
10.3390/ijms140612297
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发表时间：
2013-06-07
影响因子：
5.6
通讯作者：
Fuessel S
中科院分区：
文献类型：
--
作者：
Kunze D;Erdmann K;Froehner M;Wirth MP;Fuessel S
抗凋亡基因如Bclxl和Survivin的过表达有助于提高肿瘤细胞的存活率，并促进化疗耐药的形成。在膀胱癌细胞系EJ28和J82中，siRNA介导的Survivin基因敲除抑制了细胞的增殖，而对Bclxl的抑制使这些细胞对随后的丝裂霉素C和顺铂化疗敏感。因此，这项研究的目的是分析同时敲除Bcl-xl和Survivin是否代表了一种比单独抑制这些靶基因之一更有效的治疗膀胱癌的选择。在转染后96h，同时抑制Bclxl和Survivin对细胞活力的抑制作用较单一靶点处理(最多可减少29%)更明显(下降40%~48%)。此外，同时下调Bclxl和Survivin基因可显著提高后续化疗的疗效。例如，经Bclxl和Survivin抑制加顺铂治疗后，EJ28细胞的存活率降至6%，而单靶点siRNA加化疗仅使细胞存活率降至15%~36%。综上所述，同时siRNA介导的抑制抗细胞凋亡的BclxL和Survivin的基因敲除-一种基于多靶点分子的治疗-与传统化疗相结合显示出改善膀胱癌治疗的巨大潜力。
The overexpression of antiapoptotic genes, such as Bcl-xL and survivin, contributes to the increased survival of tumor cells and to the development of treatment resistances. In the bladder cancer cell lines EJ28 and J82, the siRNA-mediated knockdown of survivin reduces cell proliferation and the inhibition of Bcl-xL sensitizes these cells towards subsequent chemotherapy with mitomycin C and cisplatin. Therefore, the aim of this study was to analyze if the simultaneous knockdown of Bcl-xL and survivin might represent a more powerful treatment option for bladder cancer than the single inhibition of one of these target genes. At 96 h after transfection, reduction in cell viability was stronger after simultaneous inhibition of Bcl-xL and survivin (decrease of 40%–48%) in comparison to the single target treatments (decrease of 29% at best). Furthermore, simultaneous knockdown of Bcl-xL and survivin considerably increased the efficacy of subsequent chemotherapy. For example, cellular viability of EJ28 cells decreased to 6% in consequence of Bcl-xL and survivin inhibition plus cisplatin treatment whereas single target siRNA plus chemotherapy treatments mediated reductions down to 15%–36% only. In conclusion, the combination of simultaneous siRNA-mediated knockdown of antiapoptotic Bcl-xL and survivin—a multitarget molecular-based therapy—and conventional chemotherapy shows great potential for improving bladder cancer treatment.
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影响因子：
5.2
作者：
Kunze D;Kraemer K;Erdmann K;Froehner M;Wirth MP;Fuessel S
通讯作者：
Fuessel S
影响因子：
12.4
作者：
Seth, Shaguna;Matsui, Yoshiyuki;Polisky, Barry
通讯作者：
Polisky, Barry
影响因子：
4.8
作者：
Dohi, T;Okada, K;Altieri, DC
通讯作者：
Altieri, DC
影响因子：
8.8
作者：
Saito, T.;Hama, S.;Izumi, H.;Yamasaki, F.;Kajiwara, Y.;Matsuura, S.;Morishima, K.;Hidaka, T.;Shrestha, P.;Sugiyama, K.;Kurisu, K.
通讯作者：
Kurisu, K.
影响因子：
6.4
作者：
Kappler, M;Bache, M;Taubert, H
通讯作者：
Taubert, H