Metformin inhibits salivary adenocarcinoma growth through cell cycle arrest and apoptosis

Yuqi Guo, Tao Yu, Jian Yang, Tianqing Zhang, Yang Zhou, Fan He, Zoya Kurago, David Myssiorek, Yingjie Wu, Peng Lee, Xin Li

Research output: Contribution to journalArticle

Abstract

The inhibitory effects of metformin have been observed in many types of cancer. However, its effect on human salivary gland carcinoma is unknown. The effect of metformin alone or in combination with pp242 (an mTOR inhibitor) on salivary adenocarcinoma cells growth were determined in vitro and in vivo. We found that metformin suppressed HSY cell growth in vitro in a time and dose dependent manner associated with a reduced expression of MYC onco-protein, and the same inhibitory effect of metformin was also confirmed in HSG cells. In association with the reduction of MYC onco-protein, metformin significantly restored p53 tumor suppressor gene expression. The distinctive effects of metformin and PP242 on MYC reduction and P53 restoration suggested that metformin inhibited cell growth through a different pathway from PP242 in salivary carcinoma cells. Furthermore, the anti-tumor efficacy of metformin was confirmed in vivo as indicated by the increases of tumor necrosis and reduced proliferation in xenograft tumors from metformin treated group. For the first time, the inhibitory effect of metformin on human salivary gland tumor cells was documented. Moreover, metformin inhibitory effects were enhanced by mTOR inhibitor suggesting that metformin and mTOR inhibitor utilize distinctive signaling pathways to suppress salivary tumor growth.

Original languageEnglish (US)
Pages (from-to)3600-3611
Number of pages12
JournalAmerican Journal of Cancer Research
Volume5
Issue number12
StatePublished - 2015

Keywords

  • HSG cells
  • HSY cells
  • Metformin
  • Salivary adenocarcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Guo, Y., Yu, T., Yang, J., Zhang, T., Zhou, Y., He, F., Kurago, Z., Myssiorek, D., Wu, Y., Lee, P., & Li, X. (2015). Metformin inhibits salivary adenocarcinoma growth through cell cycle arrest and apoptosis. American Journal of Cancer Research, 5(12), 3600-3611.