title: Radiosensitization effect of Huaier on breast cancer cells.
abstract: Radiotherapy is a critical treatment strategy for breast cancer. However, its wide application is sometimes restricted by radioresistance and radiotoxicity. Trametes robiniophila Murr. (Huaier), an officinal fungus used as a traditional Chinese medicine (TCM), is reported to have multi-biological functions during cancer treatment. Yet, its radiosensitization effects have not been evaluated to date. In the present study, using HTA 2.0 transcriptome microarray assay, Huaier was found to downregulate genes related to the cell cycle, cell division, cell cycle phases and DNA repair. This investigation utilized a colony formation assay to confirm the ability of Huaier to sensitize breast cancer cells to radiotherapy. Flow cytometry, immunofluorescence staining and western blotting were used to illustrate the sensitization mechanism. Our findings suggest that Huaier causes G0/G1 arrest through downregulation of cell cycle-regulating proteins in MCF-7 and MDA-MB-468 cells, prolongs the persistence of γ-H2Ax foci after radiotherapy and interferes with the homologous recombination (HR) pathway of DNA repair by downregulating RAD51. These results suggest that Huaier has the ability to sensitize breast cancer cells to radiotherapy through regulation of the cell cycle and DNA repair pathway. Thus, Huaier may be a promising radiosensitizer for the treatment of breast cancer.
authors.affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Laboratory Medicine Center, Qilu Hospital of Shandong University (Qingdao), Qingdao, Shandong 266035, P.R. China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey and Rutgers - Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Haffty
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Meena S
authors.initials: MS
authors.lastname: Moran
mesh_terms: D001943:Breast Neoplasms / Q000532:radiotherapy*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D008516:Medicine, Chinese Traditional; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D055454:Trametes / Q000737:chemistry*
chemical_list: D011838:Radiation-Sensitizing Agents