Li Zheng, Zhang Tian-Biao, Jia Dong-Hui, Sun Wen-Qi, Wang Chao-Liang, Gu Ao-Zheng, Yang Xiao-Ming
Department of Urology, Nanyang City Center Hospital, Nanyang, Henan 473009, P.R. China.
Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Oncol Lett. 2018 Feb;15(2):2619-2624. doi: 10.3892/ol.2017.7588. Epub 2017 Dec 11.
Genipin, a natural compound derived from the fruit of , possesses numerous biological properties. The aim of the present study was to investigate the anticancer effects of genipin in human bladder cancer. T24 and 5637 bladder cancer cells were treated with different concentrations of genipin (0-200 µM) and tested for cell viability, colony formation, cell cycle progression and apoptosis. A xenograft model of bladder cancer was established to determine the anticancer effect of genipin . The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of genipin was examined. Genipin treatment significantly inhibited the viability and clonogenic growth of bladder cancer cells and inhibited the growth of T24 xenograft tumors, compared with vehicle controls (P<0.05). Genipin-treated cells exhibited a cell cycle arrest at the G0/G1-phase, which was accompanied by a deregulation of numerous cell cycle regulators. Genipin-treated cells demonstrated a significant increase in the percentage of apoptotic cells, loss of mitochondrial membrane potential, Bax translocation to the mitochondria and the release of cytochrome to the cytosol. Additionally, genipin treatment significantly (P<0.05) reduced the phosphorylation levels of PI3K and Akt in bladder cancer cells. Importantly, genipin-mediated anticancer effects were reversed by the overexpression of constitutively active Akt. In conclusion, to the best of our knowledge, the present study demonstrates for the first time the growth inhibitory effects of genipin in bladder cancer cells, and indicates its potential as a natural anticancer agent for bladder cancer.
京尼平是一种从栀子果实中提取的天然化合物，具有多种生物学特性。本研究的目的是探讨京尼平对人膀胱癌的抗癌作用。用不同浓度的京尼平（0 - 200 μM）处理T24和5637膀胱癌细胞，并检测细胞活力、集落形成、细胞周期进程和细胞凋亡。建立膀胱癌异种移植模型以确定京尼平的抗癌作用。检测磷酸肌醇-3激酶（PI3K）/Akt信号通路在京尼平作用中的参与情况。与溶剂对照组相比，京尼平处理显著抑制了膀胱癌细胞的活力和克隆生长，并抑制了T24异种移植瘤的生长（P<0.05）。经京尼平处理的细胞在G0/G1期出现细胞周期阻滞，同时伴有多种细胞周期调节因子的失调。经京尼平处理的细胞凋亡细胞百分比显著增加，线粒体膜电位丧失，Bax转位至线粒体，细胞色素c释放至胞质溶胶。此外，京尼平处理显著（P<0.05）降低了膀胱癌细胞中PI3K和Akt的磷酸化水平。重要的是，组成型活性Akt的过表达逆转了京尼平介导的抗癌作用。总之，据我们所知，本研究首次证明了京尼平对膀胱癌细胞的生长抑制作用，并表明其作为膀胱癌天然抗癌剂的潜力。
