EGFR inhibitor enhances cisplatin sensitivity of oral squamous cell carcinoma cell lines
EGFR inhibitor enhances cisplatin sensitivity of oral squamous cell carcinoma cell lines
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DOI：
10.1007/s12253-008-9020-5
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发表时间：
2008-03-01
影响因子：
2.8
通讯作者：
Fujita, Shigeyuki
中科院分区：
文献类型：
--
作者：
Hiraishi, Yukihiro;Wada, Takeshi;Fujita, Shigeyuki
表皮生长因子受体（EGFR）参与癌细胞生物学的多个方面。EGFR已被确定为癌症治疗的重要靶点，目前各种EGFR抑制剂用于治疗多种人类癌症。最近，EGFR及其下游信号通路被确定为与顺铂敏感性相关。此外，EGFR抑制剂已显示出对基于顺铂的治疗失败的患者的显著前景。在这项研究中，我们调查了EGFR抑制剂治疗是否提高口腔鳞状细胞癌（OSCC）细胞系对顺铂的敏感性。AG 1478，一种特异性EGFR酪氨酸激酶抑制剂，与顺铂的组合的效果进行了评价，在培养的口腔鳞癌细胞系和顺铂耐药亚系。EGFR和p-EGFR在两种顺铂耐药细胞系中的表达均高于相应的亲本细胞系。此外，在两种细胞系中发现AG 1478与顺铂的组合对OSCC细胞生长的抑制增强。这些结果表明，EGFR抑制剂和顺铂的组合可能是有用的作为一个合理的策略，用于治疗口腔癌患者获得性顺铂耐药。
Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer cell biology. EGFR has already been identified as an important target for cancer therapy, with various kinds of EGFR inhibitors currently used in treatment of several human cancers. Recently, EGFR and its downstream signaling pathways were identified as being associated with cisplatin sensitivity. In addition, EGFR inhibitors have shown significant promise for patients who failed cisplatin-based therapy. In this study, we investigated whether treatment with an EGFR inhibitor improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines. The effects of a combination of AG1478, a specific EGFR tyrosine kinase inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in the two cisplatin-resistant cell lines compared with the corresponding parental cell lines. In addition, augmented inhibition of OSCC cell growth by the combination of AG1478 with cisplatin was found in both cell lines. These results suggest that the combination of an EGFR inhibitor and cisplatin may be useful as a rational strategy for the treatment of patients with oral cancer with acquired cisplatin resistance.