Silencing HER3 Radiosensitizes Luminal A Breast Cancer Cells

【Objective】Endocrine therapy and local radiotherapy are the main treatments for Luminal A breast cancer.However,drug resistance and distant metastasis happened during long-term treatment.Some studies have found that drug resistance and distant metastasis may be related to HER3 over-expression.The purpose of this study is to elucidate the effect of HER3 in radiotherapy resistance and further assess whether HER3 can be a potential target for radiosensitivity.【Methods】We used retroviruses to construct stable low-expression of HER3 in Luminal A breast cancer cells(MCF-7 and ZR75-1).CCK-8 assay was used to observe the change of proliferation in different groups.Colony-forming assay was used to detect differences in radiosensitivity.Flow cytometry was used to detect cell cycle and apoptosis.Immunofluorescence assay was used to detect the number of γH2AX foci in the nucleus after ionizing radiation(IR).Western blot was used to verify the change of relative proteins.The nude mice xenograft model was used to observe the growth of tumor-bearing mice and transplanted tumors in vivo.【Result】 In our study,silencing HER3 reduced cells proliferation and clone formation ability after IR.That meant silencing HER3 increased the sensitivity of luminal A breast cancer cells to radiotherapy.Radiosensitivity mechanisms could be that silencing HER3 enhanced radiation-induced DNA damage and reduced DNA repair.Then silencing HER3 increased IR-induced apoptosis and G2/M arrest.In addition,silencing HER3 inhibited IR-induced migration and invasion.At the same time,silencing HER3 inhibited the growth of tumor-bearing mice and xenografts,and the effect was more obvious when combined with IR in vivo.【Conclusion】Silencing HER3 could significantly increase the radiosensitivity of Luminal A breast cancer cells and HER3 could be a potential target for radiotherapy.