RRC ID 54711
Author Sekino N, Kano M, Matsumoto Y, Sakata H, Murakami K, Toyozumi T, Otsuka R, Yokoyama M, Shiraishi T, Okada K, Kamata T, Ryuzaki T, Matsubara H.
Title The Antitumor Effects of Metformin on Gastric Cancer In Vitro and on Peritoneal Metastasis.
Journal Anticancer Res.
Abstract BACKGROUND/AIM:Gastric cancer (GC) with peritoneal metastasis remains difficult to treat. The anti-diabetic drug metformin exerts various antitumor effects via the 5'-adenosine monophosphate-activated protein kinase (AMPK) pathway and nuclear factor-kappa B (NF-ĸB). Therefore, we evaluated the antitumor effects of metformin for GC in vitro and on peritoneal metastasis.
MATERIALS AND METHODS:The human GC cell lines MKN1, MKN45, KATO-III and SNU-1 were used. The antiproliferative effect was evaluated in vitro with 0.5 mM or 25 mM glucose and in vivo using tumor xenograft peritoneal models of metastasis. The protein expression of AMPK, liver kinase B1 (LKB1) and NF-ĸB in tumors was examined by western blotting.
RESULTS:Metformin inhibited cell proliferation in all GC lines and sensitivity was increased under low-glucose conditions in vitro. Metformin also suppressed peritoneal metastasis. In tumors, metformin reduced the numbers of proliferating cells and NF-ĸB expression, but a similar trend was not noted for AMPK.
CONCLUSION:Metformin may be a useful drug for the treatment of GC with peritoneal metastasis.
Volume 38(11)
Pages 6263-6269
Published 2018-11
DOI 10.21873/anticanres.12982
PII 38/11/6263
PMID 30396946
MeSH Adenylate Kinase / metabolism Animals Antineoplastic Agents / administration & dosage* Antineoplastic Agents / pharmacology Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects Gene Expression Regulation, Neoplastic / drug effects Humans Metformin / administration & dosage* Metformin / pharmacology Mice NF-kappa B / metabolism Peritoneal Neoplasms / drug therapy* Peritoneal Neoplasms / metabolism Peritoneal Neoplasms / secondary* Protein-Serine-Threonine Kinases / metabolism Stomach Neoplasms / drug therapy* Stomach Neoplasms / metabolism Treatment Outcome Xenograft Model Antitumor Assays
Resource
Human and Animal Cells MKN1(RCB1003) MKN45(RCB1001) Kato III(RCB2088)