Abstract 3492: Metformin inhibits salivary gland tumor growth through cell cycle arrest and apoptosis

Human salivary gland cancer (SGC) is one of the common malignancies found in the head and neck area. The limitation of the treatment and poor prognosis are calling for more investigations into novel intervention to improve the treatment modality in SGCs. Metformin as a widely used anti-type-2 diabetes medicine had demonstrated its anti-tumor potential in many different types of cancers. Our previous work demonstrated that metformin effectively targeted c-Myc oncogene to prevent the initiation and progression of prostate cancer. Interestingly, the overexpression of c-Myc has also been shown in some SGCs, such as salivary gland adenoid cystic carcinoma. Therefore, it is intriguing to explore metformin9s anti-neoplastic efficacy of metformin in SGC. In this study, we used a human salivary adenocarcinoma cell line, HSY cell line as a model for salivary gland tumor. Our in vitro results show metformin prominently suppresses the growth of HSY cell through stimulation of cell cycle arrest and apoptosis. Meanwhile, metformin significantly down-regulates cMyc expression and rescues p53 tumor suppressor gene expression. Considering that mTOR inhibitors resistance could occur when tumors over-express cMYC. PP242, a novel and potent mTOR inhibitor was used in combination with metformin to inhibit HSY cell growth. As expected, metformin enhanced the inhibitory effects of PP242 associated with reduced c-MYC levels in vitro. Further in HSY xenograft tumors, massive necrotic areas were observed inside the tumors from metformin treated mice while only limited necrotic area in the core of tumors from PBS treated mice. Staining of proliferation marker Ki-67 confirmed lower proliferation rate in tumors from metformin treated group compare to that from the PBS group. In conclusion, our novel finding of metformin efficacy in SGC not only proves metformin plays a pivotal role in suppressing SGCs through cell cycle arrest and apoptosis, but also suggest that a combination treatment using metformin and mTOR inhibitors together may yield better inhibitory efficacy. Citation Format: Yuqi Guo. Metformin inhibits salivary gland tumor growth through cell cycle arrest and apoptosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3492. doi:10.1158/1538-7445.AM2015-3492