Endostar down-regulates HIF-1 and VEGF expression and enhances the radioresponse to human lung adenocarcinoma cancer cells

Mol Biol Rep (2012) 39:8995 DOI 10.1007/s11033-011-0713-6

Endostar down-regulates HIF-1 and VEGF expressionand enhances the radioresponse to human lung adenocarcinoma cancer cells

Ling Zhang Wei Ge Ke Hu YanYan Zhang ChangHu Li

XiMing Xu Du He ZhenYu Zhao JinZhong Zhang

FangFang Jie Yu Chen YongFa Zheng

Received: 9 December 2010 / Accepted: 23 April 2011 / Published online: 13 May 2011 Springer Science+Business Media B.V. 2011

Abstract To study the effect of endostar on the expression of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) and radiosensitization, the changes of A549 cells treated by endostar, radiotherapy and radiotherapy plus endostar were checked by ow cytometry (FCM), methyl thiazolyl tetrazolium (MTT), hoechst staining, and enzyme linked immunosorbent assay (ELISA). The results showed that endostar could block cell periods of A549 and stopped the cell cycle at G2/M and S periods. Cell growth inhibiting and apoptotic rate in the combination group were higher than those in other groups. Meanwhile, the levels of HIF-1 and VEGF expression in the combination group were lower than those of other groups. It suggested that endostar signicantly sensitizes the function of radiation in A549 cells by arresting the cell cycle at stage of G2/M and S, increasing the cell growth inhibiting and the apoptotic rate, down-regulating the expression of HIF-1 and VEGF.

Keywords Endostar Radioresponse HIF-1 VEGF

Lung cancer

Introduction

At present, lung cancer has become one of the malignant cancers because of the highest morbidity and mortality

worldwide, among which non-small cell lung cancer (NSCLC) accounts for about 80% of primary bronchial lung cancers. Although radiation therapy is a highly effective treatment method for NSCLC now, the outcome of monotherapy is undesirable. Therefore, how to enhance the therapeutic effect of radiotherapy remains a hot topic in the oncologic study. In addition, numerous studies have shown that inhibitor of angiogenesis enhances the efcacy of a combined treatment modality with radiotherapy [17], but the mechanism has been unclear.

Hypoxia-inducible factor 1(HIF-1) is a heterodimeric basic helix-loop-helix transcription factor composed of an O2-regulated HIF-1a and a constitutively expressed HIF-1b [8]. In the presence of oxygen, HIF-1a is hydroxylated on conserved prolyl residues within the oxygen-dependent degradation domain by prolyl hydroxylated and binds to von Hippel-Lindau protein, which in turn targets it for...