title: Metformin inhibits salivary adenocarcinoma growth through cell cycle arrest and apoptosis.
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.
authors.affiliation: Department of Basic Science and Craniofacial Biology, New York University College of Dentistry (NYUCD) New York 10010, NY, USA.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Basic Science and Craniofacial Biology, New York University College of Dentistry (NYUCD)New York 10010, NY, USA; Institute for Genomic Engineered Animal Models of Human Diseases Dalian Medical University9 West Section, South Lvshun Road, Dalian, Liaoning 116044, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Basic Science and Craniofacial Biology, New York University College of Dentistry (NYUCD) New York 10010, NY, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Basic Science and Craniofacial Biology, New York University College of Dentistry (NYUCD) New York 10010, NY, USA.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Basic Science and Craniofacial Biology, New York University College of Dentistry (NYUCD) New York 10010, NY, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Basic Science and Craniofacial Biology, New York University College of Dentistry (NYUCD) New York 10010, NY, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: He
authors.affiliation: Augusta University, Dental College of Georgia Augusta 30912, GA, USA.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Kurago
authors.affiliation: Department of Otolaryngology, New York University Langone Medical Center New York 10016, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Myssiorek
authors.affiliation: Institute for Genomic Engineered Animal Models of Human Diseases Dalian Medical University 9 West Section, South Lvshun Road, Dalian, Liaoning 116044, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathology, New York University Langone Medical CenterNew York 10016, NY, USA; Department of Urology, New York University Langone Medical CenterNew York 10016, NY, USA; Perlmutter Cancer Institute, New York University Langone Medical CenterNew York 10016, NY, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Lee
authors.affiliation: Department of Basic Science and Craniofacial Biology, New York University College of Dentistry (NYUCD)New York 10010, NY, USA; Department of Urology, New York University Langone Medical CenterNew York 10016, NY, USA; Perlmutter Cancer Institute, New York University Langone Medical CenterNew York 10016, NY, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
keywords: HSG cells; HSY cells; Salivary adenocarcinoma; metformin