Zinc enhances chemosensitivity to paclitaxel in PC-3 prostate cancer cells
Zinc enhances chemosensitivity to paclitaxel in PC-3 prostate cancer cells
复制标题
锌增强 PC-3 前列腺癌细胞对紫杉醇的化疗敏感性
DOI：
10.3892/or.2018.6622
复制
发表时间：
2018-10-01
期刊：
影响因子：
4.2
通讯作者：
Liu, Yanan
中科院分区：
文献类型：
--
作者：
Zhang, Ping;Li, Yang;Liu, Yanan
紫杉醇为基础的化疗是前列腺癌治疗的一种有前途的方法。然而，单药化疗与耐药性风险增加有关。因此，新的联合化疗方案是一个热门的研究课题。锌参与细胞凋亡的调节，例如以Zn 2+的形式和通过锌依赖性酶。锌可以诱导或抑制细胞凋亡，其作用主要取决于其浓度。已有研究表明生理浓度的锌可通过线粒体途径直接诱导PC-3前列腺癌细胞凋亡。在前列腺癌组织中，与非癌组织相比，锌浓度已被证明是降低的。此外，已证明锌的浓度随着癌症进展而进一步降低。在本研究中，研究了PC-3细胞暴露于锌是否改善了它们对化疗剂紫杉醇的敏感性。MTT实验、细胞克隆形成实验、Hoechst染色和流式细胞仪分析显示，锌增强PC-3细胞对紫杉醇的化疗敏感性。Western印迹和逆转录-聚合酶链反应被用来确定，锌/紫杉醇诱导的细胞死亡的细胞凋亡信号通路参与。本研究为开发新型肿瘤联合治疗提供了基础。
Paclitaxel-based chemotherapy is a promising approach for prostate cancer treatment. However, single-drug chemotherapy is associated with an increased risk of drug resistance. Therefore, novel combination chemotherapy regimens are a popular topic of research. Zinc participates in the regulation of apoptosis, for example in the form of Zn2+ and via zinc-dependent enzymes. Zinc can either induce or suppress apoptosis, and its effect depends primarily on its concentration. Previous research has demonstrated that physiological concentrations of zinc can directly induce apoptosis of PC-3 prostate cancer cells via the mitochondrial pathway. In prostate cancer tissues, zinc concentrations have been demonstrated to be reduced compared with non-cancerous tissues. Furthermore, the concentration of zinc has been demonstrated to decrease further with cancer progression. In the present study, it was investigated whether exposure of PC-3 cells to zinc improved their sensitivity to the chemotherapeutic agent, paclitaxel. MTT assays, cell clone formation assays, Hoechst staining and flow cytometry revealed that zinc enhanced PC-3-cell chemosensitivity to paclitaxel. Western blotting and reverse transcription-polymerase chain reaction were used to determine that the mitochondria-mediated apoptosis signaling pathway is involved with zinc/paclitaxel-induced cell death. The present study provides a foundation for the development of novel tumor combination therapy.