Adenovirus mediated p53 gene enhances the sensitivity of gastric cancer cells containing mutant-type p53 to cisplatin

Aim:To observe the effects of transfection of recombinant adenovirus mediated p53 gene (rAd-p53) on gastric cancer cells containing mutant-type p53 (mBGC-823) to cisplatin(CDDP).Methods:rAd-p53 was transfected into mBGC-823. P53 protein expression was detected by immunohistochemistry assay and Western Blot assay.mBGC-823 cells were treated with rAd-p53(5 ×109,5×1010,5×1011 vp/L),CDDP (3.125,6.25,12.50 mg/L) and combined (5×109/3.125,5×1010/6.25,5×1011/12.5 vp,mg/L). The inhibition rate of mBGC-823 cell was examined by MTT assay. Cell cycle distribution and apoptotic rate were determined by flow cytometry.Results: The single use of rAd-p53 caused P53 protein up-regulation [(63.74±4.21)% vs (30.80±5.32)%](t=-13.039,P0.001). The proliferation of mBGC-823 cells was inhibited in dose-dependent manner by rAd-p53,CDDP single or combined(P0.001).Infection of rAd-p53 induced G2/M arrest and apoptotic subpeak. After exposed to CDDP alone induced G1 arrest and apoptotic subpeak.Combined administration of rAd-p53 and CDDP remarkably arrested the cells in G2/M. Meanwhile the apoptotic rate was (51.88±2.03)% in rAd-p53+CDDP group,which was significantly higher than that in rAd-p53 group(11.76±2.33)% and CDDP group (24.70±2.42)%(F=1 620.595,P0.001).Conclusion: Infection of rAd-p53 can transfer and restore wild-type p53 gene into the gastric carcinoma cell lines with mutant p53 genetic status. rAd-p53 can increase the cellular apoptosis and chemosensitivity of gastric carcinoma cells to CDDP.