title: Effect of eIF3a on response of lung cancer patients to platinum-based chemotherapy by regulating DNA repair.
abstract: OBJECTIVE
  The purpose of this study is to test the hypothesis that eIF3a may regulate the expression of DNA repair proteins which, in turn, affects response of lung cancer patients to treatments by DNA-damaging anticancer drugs.
  
  
  METHODS
  Immunohistochemistry was used to determine the expression of eIF3a in 211 human lung cancer tissues followed by association analysis of eIF3a expression with patient's response to platinum-based chemotherapy. Ectopic overexpression and RNA interference knockdown of eIF3a were carried out in NIH3T3 and H1299 cell lines, respectively, to determine the effect of altered eIF3a expression on cellular response to cisplatin, doxorubicine, etoposide (VP-16), vincristine, and vinblastine by using MTT assay. The DNA repair capacity of these cells was evaluated by using host-cell reactivation assay. Real-time reverse transcriptase PCR and Western Blot analyses were carried out to determine the effect of eIF3a on the DNA repair genes by using cells with altered eIF3a expression.
  
  
  RESULTS
  eIF3a expression associates with response of lung cancer patients to platinum-based chemotherapy. eIF3a knockdown or overexpression, respectively, increased and decreased the cellular resistance to cisplatin and anthrocycline anticancer drugs, DNA repair activity, and expression of DNA repair proteins.
  
  
  CONCLUSIONS
  eIF3a plays an important role in regulating the expression of DNA repair proteins which, in turn, contributes to cellular response to DNA-damaging anticancer drugs and patients' response to platinum-based chemotherapy.
authors: Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiang-Ya Hospital, Central South University, Changsha, Hunan, PR China.
authors: Ji-Ye
authors: JY
authors: Yin
authors: Jie
authors: J
authors: Shen
authors: Zi-Zheng
authors: ZZ
authors: Dong
authors: Qiong
authors: Q
authors: Huang
authors: Mei-Zuo
authors: MZ
authors: Zhong
authors: De-Yun
authors: DY
authors: Feng
authors: Hong-Hao
authors: HH
authors: Zhou
authors: Jian-Ting
authors: JT
authors: Zhang
authors: Zhao-Qian
authors: ZQ
authors: Liu
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