Cancer Management and Research (Nov 2020)
The Combination of Icotinib Hydrochloride and Fluzoparib Enhances the Radiosensitivity of Biliary Tract Cancer Cells
Abstract
Linggang Zhu,1,2 Chu Zhu,1 Xuanxuan Wang,1 Hai Liu,1 Yanhong Zhu,1 Xiaonan Sun1 1Department of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Radiation Oncology, Taizhou Cancer Hospital, Taizhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiaonan SunDepartment of Radiation Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 Qingchun East Road, Hangzhou Zhejiang Province 310000, People’s Republic of ChinaTel +86 571 8609 6916Fax +86 571 8604 4817Email [email protected]: Radiotherapy and chemotherapy are the main clinical treatments for biliary tract cancers (BTCs). Patients with advanced disease have a very poor prognosis, yet no molecular targets have been proven effective for the adjuvant therapy of BTCs. In this study, we aimed to explore the effect of combination treatment with icotinib hydrochloride (IH) and fluzoparib (FZ) on radiosensitivity and clarify its underlying mechanism in the HCCC-9810 and GBC-SD human BTC cell lines.Methods: Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) assay. The cell cycle distribution and apoptosis were analyzed by flow cytometry. The phosphorylation of EGFR and its downstream signaling molecules and the expression of RAD51 were measured by Western blot analysis. γ-H2AX foci in the cellular nuclei were visualized using immunofluorescence staining. A colony formation assay was performed to demonstrate cell radiosensitivity with IH and FZ combination treatment.Results: In the HCCC-9810 and GBC-SD human BTC cell lines, combined treatment with IH and FZ with synergetic radiation significantly inhibited cell proliferation, redistributed the cell cycle, enhanced apoptosis and delayed DNA damage repair by suppressing activation of the EGFR signaling pathway and attenuating expression of the homologous recombination (HR) protein RAD51.Conclusion: This study demonstrates that combined treatment with IH and FZ may be an applicable therapy to enhance the radiosensitivity of BTCs and that RAD51 may serve as a biomarker for this combination treatment.Keywords: icotinib hydrochloride, fluzoparib, biliary tract cancer, EGFR, PARP, radiotherapy
