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Cancer Lett. 2011 Aug 1;307(1):47-52. doi: 10.1016/j.canlet.2011.03.015. Epub 2011 Apr 8.

A FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells.

Author information

1
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; Oncology Center of Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, PR China.
2
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, Japan. Electronic address: m9312510@med.osaka-cu.ac.jp.
3
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan; Department of Medical Oncology, Beijing Cancer Hospital, School of Oncology, Peking University, Beijing, PR China.
4
Drug Discovery Research Laboratories, Kyowa Hakko Kirin Co., Ltd., Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
5
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.

Abstract

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.

PMID:
21482024
DOI:
10.1016/j.canlet.2011.03.015
[Indexed for MEDLINE]

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