HER2 overexpression in breast cancer cells reduces the sensitivity to taxol

Aim To investigate the effects of HER2 overexpression on the chemosensitivity of breast cancer cells to taxol.Methods MTT assay was used to determine the growth inhibition of taxol in both of HER2 low-expressing MCF-7/pcDNA3.1 cells and HER2 overexpressing MCF-7/HER2 cells.The effect of taxol on cell cycle distribution in both cells was detected by flow cytometry.Annexin V-FITC/PI was performed to analyze apoptotic cells.Tumor growth inhibitory effects of taxol were examined in nude mice bearing MCF-7/pcDNA3.1 or MCF-7/HER2 xenograft.Results MTT assay showed that MCF-7/HER2 cells were more resistant than MCF-7/pcDNA3.1 cells to taxol with IC50 values of(0.074±0.012) μmol·L-1 and(0.461±0.035) μmol·L-1,respectively.Both cells were arrested at G2/M phase without significant differences after exposure to taxol.The apoptotic fraction in MCF-7/pcDNA3.1 cells was significantly higher than that inMCF-7/HER2 cells after being treated with taxol.At the dose of 5,10 and 20 mg·kg-1 taxol,tumor growth was inhibited by 36.9%,58.7% and 75.4% in nude mice bearing MCF-7/pcDNA3.1 xenograft,and inhibited by 20.1%,33.3% and 67.3% in nude mice bearing MCF-7/HER2 xenograft,respectively.Conclusions These results demonstrate that HER2 overexpression in breast cancer cells may reduce the sensitivity to taxol.