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An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells

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收录情况： ◇ SCIE

作者：
Yashiro, M.[1,2,*1] * ; Qiu, H.[1,2,3] ; Hasegawa, T.[1] ; Zhang, X.[1,4] ; Matsuzaki, T.[1] ; Hirakawa, K.[1] ;
单位： [1]Osaka City Univ, Dept Surg Oncol, Grad Sch Med, Abeno Ku, Osaka 5458585, Japan [2]Osaka City Univ, Oncol Inst Geriatr & Med Sci, Grad Sch Med, Abeno Ku, Osaka 5458585, Japan [3]Huazhong Univ Sci & Technol, Ctr Oncol, Tongji Hosp, Tongji Med Coll, Wuhan 430074, Peoples R China [4]Peking Univ, Dept Med Oncol, Beijing Canc Hosp, Sch Oncol, Beijing 100871, Peoples R China
出处：
DOI： 10.1038/bjc.2011.397
ISSN：

关键词： gastric cancer chemoresistance irinotecan EGFR inhibitor combination therapy

摘要：
BACKGROUND: Acquired drug resistance to irinotecan is one of the significant obstacles in the treatment of advanced gastric cancer. This study was performed to clarify the effect of epidermal growth factor receptor (EGFR) inhibitors in combination with SN38, an active metabolite of irinotecan, on the proliferation of irinotecan-refractory gastric cancer. METHODS: Two irinotecan-resistant gastric cancer cell lines, OCUM-2M/SN38 and OCUM-8/SN38 were, respectively, established by stepwise exposure to SN38 from the parent gastric cancer cell lines OCUM-2M and OCUM-8. The combination effects of two EGFR inhibitors, gefitinib and lapatinib, with SN38 on proliferation, apoptosis, and cell cycle on gastric cancer cells were examined. RESULTS: Gefitinib or lapatinib showed synergistic anti-tumour effects against OCUM-2M/SN38 and OCUM-8/SN38 cells when used in combination with SN38, but not against OCUM-2M or OCUM-8 cells. SN38 increased the expression of EGFR and HER2 in OCUM-2M/SN38 and OCUM-8/SN38 cells. The combination of an EGFR inhibitor and SN38 significantly increased the levels of apoptosis-related molecules, caspase-6, p53, and DAPK-2, and resulted in the induction of apoptosis of irinotecan-resistant cells. The EGFR inhibitors increased the S-phase and decreased the UGT1A1 and ABCG expression in irinotecan-resistant cells. The SN38 plus Lapatinib group more effectively suppressed in vivo tumour growth by OCUM-2M/SN38 cells than either alone group. CONCLUSION: The combination treatment with an EGFR inhibitor and irinotecan might produce synergistic anti-tumour effects for irinotecan-refractory gastric cancer cells. The regulation of SN38 metabolism-related genes and cell cycle by EGFR inhibitors might be responsible for the synergism. British Journal of Cancer (2011) 105, 1522-1532. doi:10.1038/bjc.2011.397 www.bjcancer.com Published online 13 October 2011 (C) 2011 Cancer Research UK

基金：
Japan-China Sasagawa Medical Scholarship; Foundation for Promotion of Cancer Research; KAKENHI [20591573, 22390262, 23390329]; Grants-in-Aid for Scientific Research [20591573] Funding Source: KAKEN
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外文
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中科院(CAS)分区：
出版当年[2010]版：
大类 | 2 区 医学
小类 | 3 区 肿瘤学
最新[2025]版：
大类 | 2 区 医学
小类 | 2 区 肿瘤学
JCR分区：
出版当年[2009]版：
Q1 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2009版] 出版当年五年平均 出版前一年[2008版] 出版后一年[2010版]

第一作者：
第一作者单位： [1]Osaka City Univ, Dept Surg Oncol, Grad Sch Med, Abeno Ku, Osaka 5458585, Japan [2]Osaka City Univ, Oncol Inst Geriatr & Med Sci, Grad Sch Med, Abeno Ku, Osaka 5458585, Japan [*1]Osaka City Univ, Dept Surg Oncol, Grad Sch Med, Abeno Ku, 1-4-3 Asahi Machi, Osaka 5458585, Japan
通讯作者：
通讯机构： [1]Osaka City Univ, Dept Surg Oncol, Grad Sch Med, Abeno Ku, Osaka 5458585, Japan [2]Osaka City Univ, Oncol Inst Geriatr & Med Sci, Grad Sch Med, Abeno Ku, Osaka 5458585, Japan [*1]Osaka City Univ, Dept Surg Oncol, Grad Sch Med, Abeno Ku, 1-4-3 Asahi Machi, Osaka 5458585, Japan
推荐引用方式(GB/T 7714)：
Yashiro M.,Qiu H.,Hasegawa T.,et al.An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells[J].BRITISH JOURNAL OF CANCER.2011,105(10):1522-1532.doi:10.1038/bjc.2011.397.
APA：
Yashiro, M.,Qiu, H.,Hasegawa, T.,Zhang, X.,Matsuzaki, T.&Hirakawa, K..(2011).An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells.BRITISH JOURNAL OF CANCER,105,(10)
MLA：
Yashiro, M.,et al."An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells".BRITISH JOURNAL OF CANCER 105..10(2011):1522-1532

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