Atorvastatin synergizes with IFN-纬 in treating human non-small cell lung carcinomas via potent inhibition of RhoA activity
详细信息查看全文 | 推荐本文 |
摘要
Interferon-纬 (IFN-纬) has been widely used to treat various malignant tumors including human non-small-cell-lung carcinomas (NSCLCs). However, the tumor-inhibitory effect of IFN-纬 displays not satisfactory in NSCLC treatment due to the lack of immunogenicity of NSCLCs. This study demonstrated that inhibition of RhoA activity led to significant inhibition of NSCLC cell growth accompanied by decreased expression of c-myc and cyclin D1 and increased levels of major histocompatibility complex (MHC) class I and peptide transporter protein 1 (TAP1) which are involved in tumor immunity. Combination treatment of atorvastatin and IFN-纬 resulted in a synergistic inhibition of NSCLC cell growth both in vitro and in vivo. Though IFN-纬 alone exerted minimal inhibitory effect on RhoA activity, additional administration of atorvastatin could result in a significant inhibition of RhoA activity, thus substantially suppressing NSCLC cell growth. Specifically, atorvastatin could induce specific deposition of endogenous IFN-纬 in tumors while not in other normal tissues in LLC-harbored mice. In conclusion, atorvastatin can enhance IFN-纬 sensitivity in NSCLCs both in vitro and in vivo, probably through induction of a synergistic inhibitory effect on RhoA activity. This study also suggests a potential alternative of combination of atorvastatin and IFN-纬 in clinical therapy against NSCLCs.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700