表皮生长因子受体抑制剂对口腔鳞状细胞癌的治疗及预防作用

Therapeutic and preventive effects of an epidermal growth factor receptor inhibitor on oral squamous cell carcinoma.

作者信息

Ge H, Liu H, Fu Z, Sun Z

机构信息

Department of Oral Medicine, Capital Medical University, School of Stomatology, Beijing, China.

出版信息

J Int Med Res. 2012;40(2):455-66. doi: 10.1177/147323001204000207.

DOI:10.1177/147323001204000207

PMID:22613406

Abstract

OBJECTIVE

Oral squamous cell carcinoma (OSCC) is the sixth most common human neoplasm worldwide. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is highly expressed in human OSCC and is a target for cancer therapy and prevention. This study investigated the therapeutic and preventive effects of an inhibitor of EGFR (PD153035) on OSCC.

METHODS

The effects of PD153035 were examined in human cancer cell lines in vitro, in an athymic nude mouse xenograft model in vivo, and in the 7,12-dimethyl benz[a]anthracene (DMBA)-induced hamster cheek pouch tumour model in vivo.

RESULTS

PD153035 significantly inhibited cell growth, delayed cell cycle progression and induced apoptosis in human OSCC cells in vitro. In vivo, PD153035 inhibited xenograft tumour growth in nude mice in a dose-dependent manner and prevented the development of OSCC at the postinitiation stage in the DMBA-induced hamster cheek pouch tumour model. PD153035 inhibited the DMBA-induced increases in cell proliferation and in levels of phosphorylated EGFR and phosphorylated signal transducer and activator of transcription 3 (STAT3) protein in the hamster cheek pouch.

CONCLUSIONS

Inhibitors of EGFR, such as PD153035, have potential value in the treatment and prevention of OSCC.

摘要

目的

口腔鳞状细胞癌（OSCC）是全球第六大常见人类肿瘤。表皮生长因子受体（EGFR）是一种受体酪氨酸激酶，在人类OSCC中高表达，是癌症治疗和预防的靶点。本研究调查了EGFR抑制剂（PD153035）对OSCC的治疗和预防作用。

方法

在体外人类癌细胞系、体内无胸腺裸鼠异种移植模型以及体内7,12-二甲基苯并[a]蒽（DMBA）诱导的仓鼠颊囊肿瘤模型中检测PD153035的作用。

结果

PD153035在体外显著抑制人OSCC细胞的生长，延迟细胞周期进程并诱导细胞凋亡。在体内，PD153035以剂量依赖方式抑制裸鼠异种移植肿瘤的生长，并在DMBA诱导的仓鼠颊囊肿瘤模型的起始后阶段预防OSCC的发生。PD153035抑制DMBA诱导的仓鼠颊囊中细胞增殖以及磷酸化EGFR和磷酸化信号转导子与转录激活子3（STAT3）蛋白水平的增加。