Abstract:Objective To investigate the mechanism of human epidermal growth factor receptor-3 (HER-3) gene expression on radioresistance and Apelin (APJ-endogenous ligand apelin) /APJ(G protein-coupled receptor) signaling pathway in breast cancer cells. Methods Breast cancer cells were divided into breast cancer group (MCF-7 cells in good state), blank group (MCF-7 cells + negative control lentivirus), HER-3 group (MCF-7 cells+knockdown of HER-3), F13A group ［MCF-7 cells +10 pm/ml F13A (APJ-specific antagonist)］ and combined group (MCF-7 cells +10pm/ml F13A + knockdown of HER-3). The expressions of HER-3 mRNA, cell viability and apoptosis rate were respectively detected by qRT-PCR, CCK-8 and flow cytometry. Radiosensitivity was observed by 0, 2, 4, 6 and 8 Gy radiation doses in each group. The protein expressions of Apelin13, APJ, VEGF and HIF-1α were detected by western blot, and Pearson method was used to analyze the correlation between them and HER-3. Results The mRNA expressions of HER-3 in breast cancer group, blank group, HER-3 group, F13A group and combined group were 1.00±0.00, 0.96±0.03, 0.58±0.05, 0.62±0.06 and 0.23±0.04, respectively ( F =346.100, P ＜0.01). Compared with those in breast cancer group and blank group, the activity of MCF-7 cell line in HER-3 group, F13A group and combined group statistically decreased at 24-, 48-, 72- and 96-h ( P < 0.05). There was a significant difference in apoptosis rate of MCF-7 cell lines among five groups ( F =125.200, P < 0.05), and the apoptosis rate was the highest in combined group than those of other groups ( P <0.05). When the irradiation dose was 2-, 4-, 6- and 8-Gy, the cell activity in HER-3 group, F13A group and combined group were significantly lower than that in breast cancer group and blank group ( P <0.05). Compared with breast cancer group and blank group, the protein expressions of Apeli13, APJ, VEGF and HIF-1α in HER-3 group, F13A group and combined group decreased significantly ( P <0.05). HER-3 was positively correlated with Apeli13, APJ, VEGF and HIF-1α ( P <0.05), respectively. Conclusion Knockdown HER-3 gene can inhibit the activity of breast cancer cells, accelerate apoptosis, and increase the sensitivity of breast cancer radiotherapy to a certain extent. The mechanism may be related to the inhibition of the activity of Apelin/APJ signaling pathway.