OBJECTIVE To investigate the role of e IF3a in the regulation of DNA repair pathways in cancer chemotherapeutic response.METHODS Immunohistochemistry was used to determine the expression of e IF3a in lung and breast c...OBJECTIVE To investigate the role of e IF3a in the regulation of DNA repair pathways in cancer chemotherapeutic response.METHODS Immunohistochemistry was used to determine the expression of e IF3a in lung and breast cancer tissues followed by association analysis of e IF3a expression with patient′s response to chemotherapy.Ectopic overexpression and RNA interference knockdown of e IF3a were carried out in NIH3T3and H1299 cell lines,respectively,to determine the effect of altered e IF3a expression on cellular response to chemotherapeutic drugs by using MTT assay.The DNA repair capacity of these cells was evaluated by using host-cell reactivation,NHEJ and HR assay.Real-time reverse transcriptase PCR and Western Blot analyses were carried out to determine the effect of e IF3a on the DNA repair genes by using cells with altered e IF3a expression.RESULTS e IF3a expression associates with response of lung and breast cancer patients to platinum and anthracycline.e IF3a knockdown or overexpression,respectively,increased and decreased the cellular resistance to cisplatin and anthracycline anticancer drugs,DNA repair activity,and expression of NER and NHEJ DNA repair proteins.CONCLUSION e IF3a plays an important role in regulating the expression of NER and NHEJ DNA repair proteins which,in turn,contributes to cellular response to DNA-damaging anticancer drugs and patients′response to platinum and anthracycline chemotherapy.展开更多
基金supported by the Program for Changjiang Scholars and Innovative Research Team in University (IRT0946)Nature National Foundation of China (30873089)the Nature Science Foundation of Hunan Province, P. R. China(08JJ3058)
基金The project supported by National High-tech R&D Program of China 863 Program Grant(2009AA022704)National Natural Science Foundation of China(81573463,81173129,81202595 and NIH Grant CA 94961)
文摘OBJECTIVE To investigate the role of e IF3a in the regulation of DNA repair pathways in cancer chemotherapeutic response.METHODS Immunohistochemistry was used to determine the expression of e IF3a in lung and breast cancer tissues followed by association analysis of e IF3a expression with patient′s response to chemotherapy.Ectopic overexpression and RNA interference knockdown of e IF3a were carried out in NIH3T3and H1299 cell lines,respectively,to determine the effect of altered e IF3a expression on cellular response to chemotherapeutic drugs by using MTT assay.The DNA repair capacity of these cells was evaluated by using host-cell reactivation,NHEJ and HR assay.Real-time reverse transcriptase PCR and Western Blot analyses were carried out to determine the effect of e IF3a on the DNA repair genes by using cells with altered e IF3a expression.RESULTS e IF3a expression associates with response of lung and breast cancer patients to platinum and anthracycline.e IF3a knockdown or overexpression,respectively,increased and decreased the cellular resistance to cisplatin and anthracycline anticancer drugs,DNA repair activity,and expression of NER and NHEJ DNA repair proteins.CONCLUSION e IF3a plays an important role in regulating the expression of NER and NHEJ DNA repair proteins which,in turn,contributes to cellular response to DNA-damaging anticancer drugs and patients′response to platinum and anthracycline chemotherapy.
