Sekino Nobufumi, Kano Masayuki, Matsumoto Yasunori, Sakata Haruhito, Murakami Kentaro, Toyozumi Takeshi, Otsuka Ryota, Yokoyama Masaya, Shiraishi Tadashi, Okada Koichiro, Kamata Toshiki, Ryuzaki Takahiro, Matsubara Hisahiro
Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
Anticancer Res. 2018 Nov;38(11):6263-6269. doi: 10.21873/anticanres.12982.
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.
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.
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.
Metformin may be a useful drug for the treatment of GC with peritoneal metastasis.
背景/目的：伴有腹膜转移的胃癌（GC）仍然难以治疗。抗糖尿病药物二甲双胍通过5'-单磷酸腺苷激活蛋白激酶（AMPK）途径和核因子-κB（NF-κB）发挥多种抗肿瘤作用。因此，我们评估了二甲双胍对GC的体外抗肿瘤作用以及对腹膜转移的影响。
使用人GC细胞系MKN1、MKN45、KATO-III和SNU-1。在体外分别用0.5 mM或25 mM葡萄糖评估其抗增殖作用，并在体内使用肿瘤异种移植腹膜转移模型进行评估。通过蛋白质印迹法检测肿瘤中AMPK、肝激酶B1（LKB1）和NF-κB的蛋白表达。
二甲双胍抑制所有GC细胞系的细胞增殖，且在体外低糖条件下敏感性增加。二甲双胍还抑制腹膜转移。在肿瘤中，二甲双胍减少了增殖细胞数量和NF-κB表达，但AMPK未出现类似趋势。
二甲双胍可能是治疗伴有腹膜转移的GC的一种有效药物。
