Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway

Xie,Jinlin; Lin,Wenfeng; Huang,Linglong; Xu,Naijin; Xu,Abai; Chen,Binshen; Watanabe,Masami; Liu,Chunxiao; Huang,Peng

doi:10.3892/ol.2018.9111

Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway

Authors:
- Jinlin Xie
- Wenfeng Lin
- Linglong Huang
- Naijin Xu
- Abai Xu
- Binshen Chen
- Masami Watanabe
- Chunxiao Liu
- Peng Huang
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Affiliations: Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700‑8558, Japan
Published online on: July 10, 2018 https://doi.org/10.3892/ol.2018.9111
Pages: 3867-3873
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bufalin, one of the active ingredients of the Chinese drug Chan su, exhibits significant antitumor activity against various cancer types. However, the role of bufalin in renal cell carcinoma (RCC) remains unclear. In the present study, it was demonstrated that bufalin inhibited cell proliferation, blocked the cell cycle in the G2/M phase, and reduced the metastasis of human RCC ACHN cells via the upregulation of p21waf/cip1 and E‑cadherin and the downregulation of cyclin dependent kinase 1, cyclin B1, N‑cadherin, and hypoxia‑inducible factor‑1α (HIF‑1α). Further mechanistic study revealed that bufalin reduced the expression of phosphorylated (phospho)‑Akt and phospho‑mammalian target of rapamycin (mTOR). Moreover, HIF‑1α expression may be regulated through the inhibition of the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt)/mTOR signaling pathway. Thus, the present results suggest that bufalin induces cell cycle arrest and suppresses metastasis; this process may be associated with the PI3K/Akt/mTOR signaling pathway. Accordingly, it is suggested that bufalin is a therapeutic agent for RCC.

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