Li Enlai, Zhang Tao, Sun Xianchao, Li Yuan, Geng Hao, Yu Dexin, Zhong Caiyun
Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Oncol Lett. 2019 Sep;18(3):3081-3091. doi: 10.3892/ol.2019.10657. Epub 2019 Jul 24.
Cancer stem cells (CSCs) have been implicated in the genesis, progression and recurrence of renal cancer. The sonic hedgehog (Shh) pathway serves a critical role in maintaining the stemness of CSCs. Genistein, a major isoflavone component extracted from soybeans and soy products, has been demonstrated to possess anticancer activity. However, the effects of genistein on renal CSCs and its underlying mechanisms remain to be fully elucidated. The aim of the present study was to investigate the role of the Shh pathway in genistein inhibition of renal CSCs. The results of the present study demonstrated that expression levels of renal CSC markers were markedly upregulated in the sphere-forming cells, which were isolated and enriched from 786-O and ACHN cells in a tumor sphere formation assay, and more cells were arrested at the G/G phase instead of the S phase compared with the adherent cells. Furthermore, the present study demonstrated that genistein could effectively diminish the activity of renal CSCs by suppressing tumor sphere formation, decreasing renal CSCs markers, inhibiting proliferation and inducing apoptosis. Additionally, the downregulation of Shh pathway activity could inhibit renal CSCs. Genistein exhibited an inhibitory effect on renal CSCs by attenuating the activation of the Shh pathway. In conclusion, the results illustrated the role of the Shh pathway in regulating renal CSC traits and the intervention of renal CSCs by genistein, which could provide novel insights into the molecular mechanisms of renal CSC intervention.
癌症干细胞（CSCs）与肾癌的发生、发展和复发有关。音猬因子（Shh）信号通路在维持CSCs的干性中起关键作用。染料木黄酮是从大豆和豆制品中提取的主要异黄酮成分，已被证明具有抗癌活性。然而，染料木黄酮对肾CSCs的影响及其潜在机制仍有待充分阐明。本研究的目的是探讨Shh信号通路在染料木黄酮抑制肾CSCs中的作用。本研究结果表明，在肿瘤球形成试验中从786 - O和ACHN细胞中分离并富集的成球细胞中，肾CSC标志物的表达水平显著上调，与贴壁细胞相比，更多细胞停滞在G/G期而非S期。此外，本研究表明染料木黄酮可通过抑制肿瘤球形成、降低肾CSC标志物、抑制增殖和诱导凋亡有效降低肾CSCs的活性。此外，Shh信号通路活性的下调可抑制肾CSCs。染料木黄酮通过减弱Shh信号通路的激活对肾CSCs表现出抑制作用。总之，结果阐明了Shh信号通路在调节肾CSC特性中的作用以及染料木黄酮对肾CSCs的干预作用，这可为肾CSC干预的分子机制提供新的见解。
