Lapatinib inhibits the growth of esophageal squamous cell carcinoma and synergistically interacts with 5-fluorouracil in patient-derived xenograft models
Lapatinib inhibits the growth of esophageal squamous cell carcinoma and synergistically interacts with 5-fluorouracil in patient-derived xenograft models
复制标题
拉帕替尼可抑制食管鳞状细胞癌的生长，并在患者来源的异种移植模型中与 5-氟尿嘧啶产生协同相互作用。
DOI：
10.3892/or.2013.2500
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发表时间：
2013-08-01
期刊：
影响因子：
4.2
通讯作者：
Zang, Crystal Ying Qin
中科院分区：
文献类型：
--
作者：
Hou, Wenmin;Qin, Xia;Zang, Crystal Ying Qin
拉帕替尼是表皮生长因子受体（EGFR）和人EGFR-2（HER 2）酪氨酸激酶结构域的双重酪氨酸激酶抑制剂。为了探索拉帕替尼治疗食管鳞状细胞癌（ESCC）的潜在效用，我们检测了EGFR和HER 2在ESCC患者肿瘤组织和配对相邻非肿瘤组织中的表达谱。我们评估了拉帕替尼单独或与奥沙利铂或5-氟尿嘧啶（5-FU）联合对一组具有不同EGFR和HER 2表达水平的原代ESCC细胞的体外抗肿瘤作用。使用原发性ESCC异种移植模型评价拉帕替尼单独或与奥沙利铂或5-FU联合的体内作用。EGFR在80.9%（76/94）的ESCC样本中过表达，而24.5%（23/94）的样本过表达HER 2。在22.3%的样本（21/94）中检测到EGFR和HER 2共过表达。在体外，原代ESCC细胞对拉帕替尼联合5-FU或奥沙利铂比单独拉帕替尼更敏感。与拉帕替尼单独使用或与奥沙利铂联合使用相比，拉帕替尼与5-FU联合使用在原发性ESCC异种移植模型中具有更强的抗肿瘤作用，并显着降低EGFR和HER 2的磷酸化。这些数据表明，拉帕替尼在表达EGFR和/或HER 2的ESCC原代细胞中具有活性，拉帕替尼联合5-FU可能是ESCC患者有希望的治疗策略。
Lapatinib is a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) tyrosine kinase domains. To explore the potential utility of lapatinib for the treatment of esophageal squamous cell carcinoma (ESCC), we examined the expression profiles of EGFR and HER2 in tumor tissues and in paired adjacent non-neoplastic tissues from patients with ESCC. We evaluated the antitumor effects of lapatinib alone or in combination with oxaliplatin or 5-fluorouracil (5-FU) on a panel of primary ESCC cells in vitro with various levels of EGFR and HER2 expression. The in vivo effect of lapatinib alone or in combination with oxaliplatin or 5-FU was evaluated using a primary ESCC xenograft model. EGFR was overexpressed in 80.9% (76/94) of the ESCC samples, while 24.5% (23/94) of the samples overexpressed HER2. EGFR and HER2 co-overexpression was detected in 22.3% of samples (21/94). In vitro, the primary ESCC cells were more sensitive to lapatinib combined with 5-FU or oxaliplatin than to lapatinib alone. Lapatinib in combination with 5-FU had more potent antitumor effects in the primary ESCC xenograft model, and markedly reduced the phosphorylation of EGFR and HER2, compared with lapatinib alone or in combination with oxaliplatin. These data indicate that lapatinib has activity in EGFR- and/or HER2-expressing ESCC primary cells, and that lapatinib in combination with 5-FU may be a promising treatment strategy for patients with ESCC.