Selective CDK9 knockdown sensitizes TRAIL response by suppression of antiapoptotic factors and NF-kappaB pathway.
Qian YuanKui SuShuyi LiXinyi LongLang LiuJianwu SunXin YuanMinghui YangRui TianWanting ZhangZhujie DengQuanjiang LiChanghong KeYue HeChunming ChengJingna YuanZhuohao WenWei ZhouZhengqiang YuanPublished in: Apoptosis : an international journal on programmed cell death (2023)
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.
Keyphrases
- nuclear factor
- cancer therapy
- cell cycle
- toll like receptor
- papillary thyroid
- drug delivery
- oxidative stress
- cell death
- squamous cell
- cell proliferation
- childhood cancer
- lps induced
- signaling pathway
- poor prognosis
- young adults
- inflammatory response
- immune response
- squamous cell carcinoma
- lymph node metastasis
- binding protein