The Antitumor Effects of Metformin on Gastric Cancer In Vitro and on Peritoneal Metastasis
Autor: | Ryota Otsuka, Hisahiro Matsubara, Tadashi Shiraishi, Koichiro Okada, Haruhito Sakata, Masaya Yokoyama, Yasunori Matsumoto, Masayuki Kano, Nobufumi Sekino, Takahiro Ryuzaki, Takeshi Toyozumi, Toshiki Kamata, Kentaro Murakami |
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Rok vydání: | 2018 |
Předmět: |
Cancer Research
Kinase Cell growth business.industry AMPK Cancer General Medicine medicine.disease Metformin Metastasis 03 medical and health sciences 0302 clinical medicine Oncology In vivo 030220 oncology & carcinogenesis Cancer research medicine 030211 gastroenterology & hepatology Protein kinase A business medicine.drug |
Zdroj: | Anticancer Research. 38:6263-6269 |
ISSN: | 1791-7530 0250-7005 |
Popis: | 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. |
Databáze: | OpenAIRE |
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