title: Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice.
abstract: Human cervical cancer is the fourth most common carcinoma in women worldwide. However, the emergence of drug resistance calls for continuously developing new anticancer drugs and combination chemotherapy regimens. The present study aimed to investigate the anti-cervical cancer effects of metformin, a first-line therapeutic drug for type 2 diabetes mellitus, and nelfinavir, an HIV protease inhibitor, when used alone or in combination. We found that both metformin and nelfinavir, when used alone, were moderately effective in inhibiting proliferation, inducing apoptosis and suppressing migration and invasion of human cervical cell lines HeLa, SiHa and CaSki. When used in combination, these two drugs acted synergistically to inhibit the growth of human cervical cancer cells in vitro and cervical cancer cell xenograft in vivo in nude mice, and suppress cervical cancer cell migration and invasion. The protein expression of phosphoinositide 3-kinase catalytic subunit PI3K(p110α), which can promote tumor growth, was remarkably downregulated, while the tumor suppressor proteins p53 and p21 were substantially upregulated following the combinational treatment in vitro and in vivo. These results suggest that clinical use of metformin and nelfinavir in combination is expected to have synergistic antitumor efficacy and significant potential for the treatment of human cervical cancer.
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
authors.forename: Chenglai
authors.initials: C
authors.lastname: Xia
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Jinman
authors.initials: J
authors.lastname: Chen
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Aris Pharmaceuticals Inc., Bristol, PA19007, USA.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: Guangdong Provincial Key Laboratory of Reproductive Medicine, Guangzhou, 510150, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Xiao
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.|Laboratory of Medical Molecular Virology of Ministries of Education and Health, College of Basic Medical Science, Fudan University, Shanghai, 200032, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D064593:Heterografts; D006801:Humans; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D008819:Mice, Nude; D019888:Nelfinavir / Q000008:administration & dosage / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin; D019888:Nelfinavir