Title:VE-822 Enhanced Cisplatin Chemotherapy Effects on Head and Neck
Squamous Cell Carcinoma Drug-resistant Cells
Volume: 23
Issue: 6
关键词:
化疗，顺铂，顺铂耐药，头颈部鳞状细胞癌，VE-822，p-ATR。
摘要:
Purpose: The study aimed to assess the effect of p-ATR inhibitor VE-822 in the combination
chemotherapy with cisplatin of head and neck squamous cell carcinoma and to explore the possible
mechanism.
Methods: The DNA damage levels were determined by comet assay and western blot experiments in
cisplatin-resistant and sensitive cell lines. The IC50 value changes after combination treatment with
VE-822 in cisplatin sensitive and resistant cell lines were detected by the CCK-8 test. The effects of
VE-822 combined with cisplatin on proliferation ability, colony formation ability, migration ability,
cell apoptosis and cell cycle changes were observed in vitro. In vivo, the combination treatment effect
was verified in the subcutaneous xenograft models of nude mice. Besides, the mechanism of VE-822
assisting cisplatin in chemotherapy was explored by comet assay, western blotting and immunohistochemical
experiments.
Results: The increased expression of the p-ATR protein was related to the DNA damage repair pathway
in head and neck squamous cell carcinoma cisplatin-resistant cells. VE-822 inhibited cell proliferation,
colony formation and migration abilities and improved the cisplatin chemotherapeutic effects in
subcutaneous xenograft models of nude mice by inhibiting the p-ATR expression and blocking DNA
damage repair pathway.
Conclusions: The p-ATR expression increased in head and neck squamous cell carcinoma cisplatinresistant
cells. VE-822 significantly enhanced the therapeutic effect in cisplatin resistant head and neck
squamous cell carcinoma by inhibiting p-ATR expression in vivo and in vitro.
