Killing effect of tumor-selective replicating adenovirus CNHK300 combined with paclitaxel on human breast cancer cell lines with high expression of HER-2

Objective:To evaluate the killing effect of tumor-selective replicating adenovirus CNHK300 combined with paclitaxel (chemotherapy agents) on human breast cancer cells over-expressing HER-2.Methods:The telomerase activity in breast cancer cells and MRC-5 cell line were detected semi-quantitively by TRAP-ELISA assay.Virus proliferation as- say and cell viability assay were used to evaluate the proliferation and cytolysis selectivity of CNHK300,and the results were compared with those of wtAd5.The breast cancer cells were treated with CNHK300 combining paclitaxel to evaluate the killing effect of the combined regimen.Western-blot was used to detect the expression of adenovirus CNHK300 E1A in cancer and normal cells.Results:The telomerase activity of the 2 breast cancer cell lines were both positive,while telom- erase in MRC-5 fibroblast cell was negative.The proliferative ability of CNHK300 virus and its killing effect on breast cancer cells were similar to those of wtAd5.However,CNHK300 exhibited attenuated replicative ability and killing effect in normal fibroblast cell line than wtAd5 did.Combination of CNHK300 and paclitaxel exhibited increased killing effect in breast cancer cells.CNHK300 E1A was expressed in telomerase-positive breast cancer cells but not in the telomerase-neg ative normal fibroblast cells.Conclusion:CNHK300 demonstrates proliferation selectivity and killing selectivity in HER-2 over-expressed MDA-MB-453 and SK-BR-3 breast cancer cell lines,and a synergistic effect of CNHK300 combined with paclitaxel has been observed in breast cancer cells.