Journal
CANCER CELL INTERNATIONAL
Volume 19, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12935-019-0896-9
Keywords
AZD7762; Cisplatin; Osteosarcoma; Apoptosis; Chk1
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Funding
- National Natural Science Foundation of China [81472504, 81401822, 81572177]
- Science and Technology Foundation of Zhejiang Province [2016C33151]
- Medical Science and Technology Project of Zhejiang Province of China [2016146428, 2016KYA096, 2017KY071]
- Natural Science Funds of Zhejiang Province [Y17H160033, LQ14H060002, LY14H060004]
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BackgroundAZD7762 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.MethodsWe 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.ResultsIn 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 gamma H2AX expression.ConclusionThese 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.
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