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

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

  • Apoptosis. 2023 Apr 15. doi: 10.1007/s10495-023-01842-4.
Qian Yuan # 1,  Kui Su # 1,  Shuyi Li # 1,  Xinyi Long 1,  Lang Liu 1,  Jianwu Sun 1,  Xin Yuan 1,  Minghui Yang 1,  Rui Tian 1,  Wanting Zhang 1,  Zhujie Deng 1,  Quanjiang Li 1,  Changhong Ke 1,  Yue He 2,  Chunming Cheng 2,  Jingna Yuan 2,  Zhuohao Wen 2,  Wei Zhou 3,  Zhengqiang Yuan 4
Affiliations

Affiliations

  • 1 School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China.
  • 2 Jinhang Bio-Science and Biotechnology Co. Ltd, Guangzhou, 510630, People's Republic of China.
  • 3 School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China. zhou_wei@gdut.edu.cn.
  • 4 School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 510006, People's Republic of China. yuanzq@gdut.edu.cn.
  • # Contributed equally.
PMID: 37060507 DOI: 10.1007/s10495-023-01842-4
Abstract

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.

Keywords

CDK9 silencing; Cancer therapy; DR5; NF-κB; TRAIL-resistance.

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