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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3867-3873
Number of pages7
JournalOncology Letters
Volume16
Issue number3
DOIs
Publication statusPublished - Sep 1 2018

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1-Phosphatidylinositol 4-Kinase
Sirolimus
Renal Cell Carcinoma
Neoplasm Metastasis
Hypoxia-Inducible Factor 1
Cadherins
CDC2 Protein Kinase
Cyclin B1
Proto-Oncogene Proteins c-akt
G2 Phase
Cell Cycle Checkpoints
Cell Division
bufalin
Cell Cycle
Up-Regulation
Down-Regulation
Cell Proliferation
Pharmaceutical Preparations
Neoplasms

Keywords

  • Bufalin
  • Cycle arrest
  • Metastasis
  • p-Akt
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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.

In: Oncology Letters, Vol. 16, No. 3, 01.09.2018, p. 3867-3873.

Research output: Contribution to journalArticle

Xie, Jinlin ; Lin, Wenfeng ; Huang, Linglong ; Xu, Naijin ; Xu, Abai ; Chen, Binshen ; Watanabe, Masami ; Liu, Chunxiao ; Huang, Peng. / Bufalin suppresses the proliferation and metastasis of renal cell carcinoma by inhibiting the PI3K/Akt/mTOR signaling pathway. In: Oncology Letters. 2018 ; Vol. 16, No. 3. pp. 3867-3873.
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