Gan Yu, Chen Qing, Lei Yan
Qingshan Clinic, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.
Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Oncol Lett. 2017 Oct;14(4):4977-4982. doi: 10.3892/ol.2017.6793. Epub 2017 Aug 23.
Taxol is the first-line chemotherapeutic agent for patients with castration-resistant prostate cancer. However, the mechanism of the sensitivity of prostate cancer cells to Taxol treatment remains to be elucidated. In the present study, it was found that paclitaxel induced more apoptosis and maspin expression in phosphatase and tensin homolog (PTEN)-positive 22Rv1 cells than PTEN-negative LNCaP cells. Knockdown of PTEN in 22Rv1 cells resulted in increased resistance to paclitaxel and impaired the induction of maspin expression by paclitaxel. Overexpression of PTEN sensitized LNCaP cells to paclitaxel treatment and increased maspin induction by paclitaxel. Furthermore, knocking down maspin abrogated PTEN-induced paclitaxel sensitivity in LNCaP cells. PTEN/maspin signaling may be important for regulating the susceptibility to paclitaxel in prostate cancer.
紫杉醇是去势抵抗性前列腺癌患者的一线化疗药物。然而,前列腺癌细胞对紫杉醇治疗敏感性的机制仍有待阐明。在本研究中,发现紫杉醇在磷酸酶和张力蛋白同源物(PTEN)阳性的22Rv1细胞中比PTEN阴性的LNCaP细胞诱导更多的细胞凋亡和maspin表达。在22Rv1细胞中敲低PTEN导致对紫杉醇的抗性增加,并削弱了紫杉醇对maspin表达的诱导作用。PTEN的过表达使LNCaP细胞对紫杉醇治疗敏感,并增加了紫杉醇对maspin的诱导作用。此外,敲低maspin消除了PTEN诱导的LNCaP细胞对紫杉醇的敏感性。PTEN/maspin信号传导可能对调节前列腺癌对紫杉醇的敏感性很重要。