靶向抑制CDK12/13在高级别胶质瘤中的体外治疗效果和作用分子机制探究

梅艳青, 韩雨洁, 翁文筠, 张蕾, 唐玉杰

In vitro therapeutic effects and molecular mechanisms of targeted inhibition of CDK12/13 in high-grade gliomas

MEI Yanqing, HAN Yujie, WENG Wenyun, ZHANG Lei, TANG Yujie

图5 靶向抑制CDK12/13通过显著下调GBM和DIPG细胞DDR相关基因的转录引起DNA损伤的积累 Note： A. RT-qPCR results showed that SR-4835 or THZ531 treatment for 20 h had effects on the expression of genes related to DNA damage repair in DIPG17, SF188, and U251 cell lines. B. Western blotting results showed the effect of SR-4835 and THZ531 treatment on protein levels of γH2AX and RNA Pol Ⅱ S2P in DIPG17, SF188, and U251 cell lines. ①P=0.001 8, 0.1 μmol/L SR4835 versus DMSO; ②P>0.05, 0.1 μmol/L SR4835 versus DMSO. Except for the P values shown in ① and ②, all other P values are less than 0.000 1 (0.1 μmol/L or 1 μmol/L SR4835 versus DMSO, 0.5 μmol/L or 5 μmol/L THZ531 versus DMSO).

Fig 5 Targeted inhibition of CDK12/13 induced accumulation of DNA damage by significantly down-regulating transcription of genes involved in DDR in GBM and DIPG cells