Abstract:
Objective To investigate the effect of human epidermal growth factor receptor 2 (HER2) on apoptosis and invasion of ovarian cancer A2780 and SKOV3 cells and its mechanism.
Methods A total of 27 pairs of ovarian tissues and paracancerous tissues were collected from 27 ovarian cancer patients. Ovarian cancer cells (A2780 cells and SKOV3 cells) and ovarian epithelial cells HOSEpiC were selected as experimental cells. Real-time quantitative polymerase chain reaction (qRT-PCR), Western blot and immunohistochemical techniques were used to detect the expression levels of HER2, E74-like ETS transcription factor 3 (ELF3), sonic hedgehog (SHH) and GLIS family zinc finger protein 1 (GLI1); cell viability, apoptotic rate and invasive ability of A2780 and SKOV3 cells were analyzed by cell counting kit-8 (CCK-8), flow cytometry and Transwell assay, respectively.
Results HER2 protein and HER2 mRNA expression were higher in ovarian cancer tissues than in paracancerous tissues, the expression of HER2 protein in A2780 cells and SKOV3 cells was higher than that in HOSEPiC cells(P < 0.05). In A2780 and SKOV3 cells, compared with cells transfected with si-NC, the expression level of HER2 protein was decreased in cells transfected with si-HER2, and the cell viability was decreased, the cell apoptosis rate was increased, and the number of invasive cells was decreased (P < 0.05). In A2780 and SKOV3 cells, the expression of ELF3 mRNA in cells transfected with si-HER2 was lower than that in cells transfected with si-NC, and the expression of ELF3 mRNA in cells transfected with si-HER2+ELF3 was higher than that in cells transfected with si-HER2+pcDNA (P < 0.05). Compared with cells transfected with si-NC, the viability of cells transfected with si-HER2 decreased, the apoptosis rate increased, and the number of invasive cells decreased (P < 0.05). Compared with cells transfected with si-HER2+pcDNA, cells transfected with si-HER2+ELF3 had increased viability, decreased apoptosis rate and increased number of invasion cell (P < 0.05). In A2780 and SKOV3 cells, the expression of SHH and GLI1 protein in cells transfected with si-HER2 was lower than that in cells transfected with si-NC, and the expression of SHH and GLI1 protein in cells transfected with si-HER2+ELF3 was higher than that in cells transfected with si-HER2+pcDNA (P < 0.05).
Conclusion HER2 silencing can promote ovarian cancer cell apoptosis and inhibit cell invasion by regulating the ELF3/SHH pathway, which suggests that inhibition of HER2 expression might be an effective strategy for the treatment of ovarian cancer.