PURPOSE: Ku70 protein is involved in DNA double-strand break repair,V(D)J recombination and chemoresistance. In this study, we investigated the role of Ku70 in the chemoresistance of lung cancer and the potential of Ku70 small-interfering RNA (siRNA) as a therapy for reversal of cisplatin resistance.
METHODS: Ku70 mRNA and protein expression levels were investigated by reverse transcription PCR and western blot analyses, respectively. Ku70-specific siRNA was synthesized and transfected into cisplatin-resistant human lung adenocarcinoma cell line A549/DDP prior to treatment with cisplatin. Cell survival was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis was assessed using flow cytometry analysis. Caspase-3 activity was detected by spectrophotometer.
RESULTS: The Ku70mRNA and protein expression were significantly elevated in A549DDP cells compared with those in parental A549 cells. Ku70-specific siRNA enhanced the sensitivity of A549/DDP cells to cisplatin, along with increased activity of caspase-3,increased cell apoptosis, declined mitochondrial membrane potential and arrested S phase of cell cycle.
CONCLUSIONS: Ku70 might be involved in the chemoresistance of lung cancer.Ku70-specific siRNA induced sensitivity to cisplatin treatment in cisplatin-resistant A549/DDP cells and increased cell apoptosis was invovled.
CLINICAL IMPLICATIONS: Ku70 may be one marker of chemoresistance for lung cancer.Combination treatment with Ku70 siRNA and cisplatin may overcome cisplatin resistance and enhance therapeutic efficacy.
DISCLOSURE: The following authors have nothing to disclose: Jie Zhang, Ke Wang, Ping Li, Yarong Li
No Product/Research Disclosure Information