Lapatinib acts on gastric cancer through both antiproliferative function and augmentation of trastuzumab-mediated antibody-dependent cellular cytotoxicity

被引：28

作者：

Shiraishi, Kensuke ^{[1
]}

Mimura, Kousaku ^{[2
]}

Izawa, Shinichiro ^{[1
]}

Inoue, Ayako ^{[1
]}

Shiba, Shugo ^{[1
]}

Maruyama, Takanori ^{[1
]}

Watanabe, Mitsuaki ^{[1
]}

Kawaguchi, Yoshihiko ^{[1
]}

Inoue, Masayuki ^{[1
]}

Fujii, Hideki ^{[1
]}

Kono, Koji ^{[2
,3
]}

机构：

[1] Univ Yamanashi, Dept Surg 1, Kofu, Yamanashi, Japan

[2] Natl Univ Singapore, Dept Surg, Singapore 119228, Singapore

[3] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore

来源：

GASTRIC CANCER | 2013年 / 16卷 / 04期

关键词：

Gastric cancer; HER2; Lapatinib; Trastuzumab; ADCC; TYROSINE-KINASE-INHIBITOR; METASTATIC BREAST-CANCER; EPIDERMAL-GROWTH-FACTOR; DUAL EGFR; IN-VITRO; CELLS; THERAPY; HER2; RECEPTOR; GW572016;

D O I：

10.1007/s10120-012-0219-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Trastuzumab has been recently approved for clinical use to treat HER2-expressing advanced gastric cancer, and anti-HER2-targeting therapy has become a promising option for gastric cancer. Lapatinib is a dual tyrosine kinase inhibitor targeting EGFR and HER2. The aim of the present study was to explore the utility of lapatinib for gastric cancer, with a particular focus on trastuzumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Nine gastric cancer cell lines were evaluated for the effects of lapatinib on the cell-surface accumulation of HER2 and analyzed for their additional effects on trastuzumab-mediated ADCC. Also, HER2 signaling with Western blot, proliferative function with the MTT assay, and apoptosis-inducing activity with 7ADD/Annexin-V were investigated when a panel of gastric cancer cell lines was treated with lapatinib. Lapatinib inhibited HER2 signaling and cell proliferation in the panel of gastric cancer cell lines. Lapatinib also induced the accumulation of HER2 on the cell surface, resulting in the enhancement of trastuzumab-mediated ADCC of gastric cancer. Lapatinib exhibits inhibitory activity in gastric cancer cells, and the combination of lapatinib with trastuzumab may be a promising treatment strategy for gastric cancer patients.

引用

页码：571 / 580

页数：10

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