Selective CDK9 knockdown sensitizes TRAIL response by suppression of antiapoptotic factors and NF-kappaB pathway.

Autor: Yuan, Qian, Su, Kui, Li, Shuyi, Long, Xinyi, Liu, Lang, Sun, Jianwu, Yuan, Xin, Yang, Minghui, Tian, Rui, Zhang, Wanting, Deng, Zhujie, Li, Quanjiang, Ke, Changhong, He, Yue, Cheng, Chunming, Yuan, Jingna, Wen, Zhuohao, Zhou, Wei, Yuan, Zhengqiang
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Zdroj: Apoptosis; Aug2023, Vol. 28 Issue 7/8, p1060-1075, 16p
Abstrakt: The aberrantly up-regulated CDK9 can be targeted for cancer therapy. The CDK inhibitor dinaciclib (Dina) has been found to drastically sensitizes cancer response to TRAIL-expressing extracellular vesicle (EV-T). However, the low selectivity of Dina has limited its application for cancer. We propose that CDK9-targeted siRNA (siCDK9) may be a good alternative to Dina. The siCDK9 molecules were encapsulated into EV-Ts to prepare a complexed nanodrug (siEV-T). It was shown to efficiently suppress CDK9 expression and overcome TRAIL resistance to induce strikingly augmented apoptosis in lung cancer both in vitro and in vivo, with a mechanism related to suppression of both anti-apoptotic factors and nuclear factor-kappa B pathway. Therefore, siEV-T potentially constitutes a novel, highly effective and safe therapy for cancers. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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