The BET bromodomain inhibitor JQ1 radiosensitizes non-small cell lung cancer cells by upregulating p21

Publication date: 10 April 2017
Source:Cancer Letters, Volume 391
Author(s): Jian Wang, Ye Wang, Hong Mei, Zhongyuan Yin, Yuanyuan Geng, Tao Zhang, Gang Wu, Zhenyu Lin
Radiotherapy is an important treatment modality in the management of locally advanced non-small cell lung cancer (NSCLC). However, radioresistance markedly impairs its efficacy in clinic. Bromodomain and extra-terminal (BET) bromodomain inhibitors have demonstrated dramatic antitumor activity in several preclinical human cancer models. In this study, we investigated for the first time the effect of JQ1, a novel BET bromodomain inhibitor, on tumor cell radiosensitivity of NSCLC in vitro and in vivo. Our results demonstrated that JQ1 significantly enhanced the effect of irradiation in NSCLC cell lines through a c-myc-independent mechanism. The notable findings in response to this combined treatment were prolonged delay in IR-induced DNA double-strand break (DSB) repair, induced robust G2/M checkpoint arrest and increased cell apoptosis. Additional investigations revealed that induction of p21 played an important role in its radiosensitizing effects. In conclusion, these results suggested that BET bromodomain inhibition might offer a potential strategy for enhancing the effects of radiotherapy and reducing radioresistance.



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