单位：[1]Osaka City Univ, Grad Sch Med, Dept Surg Oncol, Abeno Ku, Osaka 5458585, Japan[2]Osaka City Univ, Grad Sch Med, Oncol Inst Geriatr & Med Sci, Abeno Ku, Osaka 5458585, Japan[3]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Ctr Oncol, Wuhan 430074, Peoples R China肿瘤科华中科技大学同济医学院附属同济医院[4]Peking Univ, Sch Oncol, Beijing Canc Hosp, Dept Med Oncol, Beijing 100871, Peoples R China[5]Kyowa Hakko Kirin Co Ltd, Drug Discovery Res Labs, Shizuoka, Japan
Aim: The aim of this study was to clarify the ability of a FGFR2 inhibitor, Ki23057, to enhance the chemosensitivity of drug-resistant gastric cancer cell lines when used in combination with chemotherapeutic drugs. Materials and methods: Five cancer cell lines resistant to irinotecan (SN38), paclitaxel (PTX), etoposide (VP16), oxaliplatin (OXA), and gemcitabine (GEM) were respectively established from a parent gastric cancer cell line, OCUM-2M, and were named OCUM-2M/SN38, OCUM-2M/PTX, OCUM-2M/VP16, OCUM-2M/OXA, and OCUM-2M/GEM. The effects of the combination of Ki23057 with anticancer drugs on proliferation, apoptosis, and mRNA expression were examined. Results: Ki23057 significantly decreased the IC(50) values of OCUM-2M/SN38, OCUM-2M/PTX, and OCUM-2M/VP16, but not those of OCUM-2M/OXA and OCUM-2M/GEM. Ki23057 significantly enhanced the apoptosis rates induced by chemotherapeutic drugs in both the drug-resistant cell lines and the parental cell line. Ki23057 decreased the ERCC1 expression level in OCUM-2M/SN38, OCUM-2M/PTX, and OCUM-2M/VP16. Ki23057 increased the p53 expression level in OCUM-2M/SN38 and OCUM-2M/PTX, but not in OCUM-2M/VP16. Conclusion: The FGFR2 inhibitor Ki23057 might be therapeutically promising for treating drug-resistant gastric cancer cells, especially when used in combination with SN38, PTX, or VP16. The apoptosis process might be the main mechanism underlying the synergistic effect of these combinations. The ERCC1 and p53 genes may play an integral role in the synergism between Ki23057 and chemotherapeutic agents in drug-resistant cell lines. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
基金：
KAKENHI [22390262, 20591573]; Japan-China Sasagawa Medical Scholarship; Grants-in-Aid for Scientific Research [20591573, 22390262] Funding Source: KAKEN
第一作者单位：[1]Osaka City Univ, Grad Sch Med, Dept Surg Oncol, Abeno Ku, Osaka 5458585, Japan[3]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Ctr Oncol, Wuhan 430074, Peoples R China
通讯作者：
通讯机构：[1]Osaka City Univ, Grad Sch Med, Dept Surg Oncol, Abeno Ku, Osaka 5458585, Japan[2]Osaka City Univ, Grad Sch Med, Oncol Inst Geriatr & Med Sci, Abeno Ku, Osaka 5458585, Japan[*1]Osaka City Univ, Grad Sch Med, Dept Surg Oncol, Abeno Ku, 1-4-3 Asahi Machi, Osaka 5458585, Japan
推荐引用方式(GB/T 7714)：
Qiu Hong,Yashiro Masakazu,Zhang Xiaotian,et al.A FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells[J].CANCER LETTERS.2011,307(1):47-52.doi:10.1016/j.canlet.2011.03.015.
APA：
Qiu, Hong,Yashiro, Masakazu,Zhang, Xiaotian,Miwa, Atsushi&Hirakawa, Kosei.(2011).A FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells.CANCER LETTERS,307,(1)
MLA：
Qiu, Hong,et al."A FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells".CANCER LETTERS 307..1(2011):47-52
医学