Kou Bo, Liu Wei, He Wenbo, Zhang Yuanyuan, Zheng Jianjie, Yan Yang, Zhang Yongjian, Xu Suochun, Wang Haichen
Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Oncol Rep. 2016 May;35(5):2880-6. doi: 10.3892/or.2016.4649. Epub 2016 Mar 3.
Tetrandrine (TET), a bisbenzylisoquinoline alkaloid found in traditional Chinese medicines, exerts anticancer activity in vitro and in vivo. However, its potential role in the prostate cancer metastatic process has not yet been elucidated. Thus, we investigated the inhibition effect of tetrandrine on prostate cancer migration and invasion and the corresponding molecular basis underlying its anticancer activity. Cell migration and invasion were determined using the Transwell chamber model. The protein expression of Akt, phosphorylated Akt, the mammalian target of rapamycin (mTOR), phosphorylated mTOR and matrix metalloproteinases 9 (MMP-9) was detected by western blot in the presence or absence of tetrandrine or in the group tetrandrine combination with LY294002 (inhibitor of Akt) and rapamycin (inhibitor of mTOR). Our studies showed that excluding the effect of tetrandrine on cell proliferation, tetrandrine significantly inhibited cell migration and invasion in prostate cancer DU145 and PC3 cells. Furthermore, tetrandrine decreased the protein levels of p-Akt, p-mTOR, and MMP-9. While the inhibition of Akt or mTOR by the respective inhibitors could potentiate this effect of tetrandrine on prostate cancer cells, the studies indicate that tetrandrine inhibits the metastasis process by negatively regulating the Akt/mTOR/MMP-9 signaling pathway. These results suggest that tetrandrine might serve as a potential metastasis suppressor to treat cancer cells that have escaped surgical removal or that have disseminated widely.
粉防己碱（TET）是一种存在于传统中药中的双苄基异喹啉生物碱，在体外和体内均具有抗癌活性。然而，其在前列腺癌转移过程中的潜在作用尚未阐明。因此，我们研究了粉防己碱对前列腺癌迁移和侵袭的抑制作用及其抗癌活性的相应分子基础。使用Transwell小室模型测定细胞迁移和侵袭。通过蛋白质印迹法检测在有或没有粉防己碱的情况下，或在粉防己碱与LY294002（Akt抑制剂）和雷帕霉素（mTOR抑制剂）联合使用的组中，Akt、磷酸化Akt、雷帕霉素靶蛋白（mTOR）、磷酸化mTOR和基质金属蛋白酶9（MMP-9）的蛋白表达。我们的研究表明，排除粉防己碱对细胞增殖的影响后，粉防己碱显著抑制前列腺癌DU145和PC3细胞的迁移和侵袭。此外，粉防己碱降低了p-Akt、p-mTOR和MMP-9的蛋白水平。虽然各自的抑制剂对Akt或mTOR的抑制可增强粉防己碱对前列腺癌细胞的这种作用，但研究表明粉防己碱通过负向调节Akt/mTOR/MMP-9信号通路抑制转移过程。这些结果表明，粉防己碱可能作为一种潜在的转移抑制因子，用于治疗那些已逃脱手术切除或已广泛播散的癌细胞。
