Zinc sensitizes prostate cancer cells to sorafenib and regulates the expression of Livin
Zinc sensitizes prostate cancer cells to sorafenib and regulates the expression of Livin
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锌使前列腺癌细胞对索拉非尼敏感并调节 Livin 的表达。
DOI：
10.1093/abbs/gmt017
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发表时间：
2013-05-01
影响因子：
3.7
通讯作者：
Song, Xishuang
中科院分区：
文献类型：
--
作者：
Chen, Xiaochi;Che, Xiangyu;Song, Xishuang
在前列腺癌发生过程中，正常的锌蓄积上皮细胞转化为不蓄积锌的恶性细胞。锌水平的增加已被证明通过caspase依赖的机制与下调的抗凋亡蛋白诱导前列腺癌细胞凋亡。我们前期的研究表明，Livin作为细胞凋亡抑制蛋白(IAPs)家族的一员，可能通过改变G1期细胞周期转变，在人类前列腺癌的发生发展过程中发挥重要作用，促进细胞增殖。在本研究中，我们测定了前列腺癌细胞对锌和索拉非尼的凋亡敏感性，发现锌对索拉非尼诱导的前列腺癌细胞凋亡具有敏化作用。令人惊讶的是，我们还发现，与Survivin和cIAP2不同的是，Livin并不是一直在减少；相反，在前列腺癌细胞48h时，它在锌诱导的凋亡中代偿性增加。我们的结果提供了潜在的治疗组合，可能会增强索拉非尼的效果，并首次揭示Livin表达增加可能在前列腺癌细胞对锌的早期细胞死亡反应中发挥作用。
In prostate carcinogenesis, normal zinc-accumulating epithelial cells are transformed into malignant cells that do not accumulate zinc. Increased levels of zinc have been shown to induce apoptosis through a caspase-dependent mechanism with down-regulated anti-apoptotic proteins in prostate cancer cells. Our previous study showed that, as a member of the inhibitor of apoptosis proteins (IAPs) family, Livin could play an important role in the initiation of human prostate cancer and promote cell proliferation by altering the G1S cell cycle transition. In the present study, we measured the apoptosis sensitivity of prostate cancer cells to zinc and sorafenib and found that zinc sensitized prostate cancer cells to sorafenib-induced apoptosis. Surprisingly, we also found that, unlike its counterparts Survivin and cIAP2, Livin was not decreased all the time; instead, it was compensatively increased in zinc-mediated apoptosis at 48 h in prostate cancer cells. Our results offer potential treatment combinations that may augment the effect of sorafenib, and also reveal, for the first time, that increased Livin expression may play a role in the early cell death response of prostate cancer cells to zinc.