Checkpoint kinase inhibitor AZD7762 enhance cisplatin-induced apoptosis in osteosarcoma cells

Cancer Cell International

Yuluan Huang¹  Chengzhen Liang²  Wei Yu²  Tao Li²  Jian Zhu²  Bing Liu²  Huimin Tao²  Hanhui Zou³ 

[1] Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University;Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University;Dept Bone & Soft Tissue Surg, Zhejiang Canc Hosp;

关键词: AZD7762;    Cisplatin;    Osteosarcoma;    Apoptosis;    Chk1;   

DOI  :  10.1186/s12935-019-0896-9

来源: DOAJ

【 摘 要 】

Abstract Background AZD7762 is a checkpoint kinase 1 (Chk 1) inhibitor, which has been reported to sensitize many tumor cells to DNA damage. However, whether AZD7762 could sensitize osteosarcoma cells to chemotherapy cisplatin has not been defined. Methods We used a variety of methods such as cell viability assays, flow cytometry, western blotting, and immunohistochemistry analysis to determine AZD7762 enhancing cisplatin-induced apoptosis on osteosarcoma cell lines in vitro and in vivo. Results In the present study, we demonstrated that AZD7762 could enhance cisplatin-mediated apoptosis and mitotic catastrophe of osteosarcoma cells in vitro, and promote the inhibition of xenograft growth induced by cisplatin in vivo. The mechanistic study indicated that AZD7762 enhance the effect of cisplatin through abrogating cisplatin-mediated G2/M arrest and inhibiting the cisplatin damage repair as demonstrated by increasing cisplatin-induced γH2AX expression. Conclusion These results suggest that AZD7762 could effectively promote cisplatin-induced apoptosis and mitotic catastrophe in osteosarcoma cells. The clinical application of AZD7762 as an adjuvant in the chemotherapy of osteosarcoma should be further explored.

【 授权许可】

Unknown