Cyclin-dependent kinase 7 inhibitor THZ2 inhibits the growth of human gastric cancer in vitro and in vivo.

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Cyclin-dependent kinase 7 inhibitor THZ2 inhibits the growth of human gastric cancer in vitro and in vivo.

Am J Transl Res. 2018;10(11):3664-3676

Authors: Huang JR, Qin WM, Wang K, Fu DR, Zhang WJ, Jiang QW, Yang Y, Yuan ML, Xing ZH, Wei MN, Li Y, Shi Z

Abstract
Cyclin-dependent kinase 7 (CDK7) is a member of the CDK family, which forms the CDK activating kinase complex with Cyclin H and RING finger protein Mat1 to control cell cycle progression and transcription by phosphorylating other CDKs and RNA polymerase II. In this study, we analyzed TCGA data and found that upregulation of CDK7 frequently occurred in human gastric cancer. A potent and selective irreversible CDK7 inhibitor THZ2 was able to induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increasing intracellular reactive oxidative species (ROS) levels in gastric cancer cells. Pretreatment with ROS scavenger N-acety-L-cysteine partially reversed cell apoptosis induced by THZ2. In the nude mice, THZ2 also suppressed the growth of xenograft tumors of gastric cancer. Overall, our data showed that inhibition of CDK7 with THZ2 in gastric cancer presented outstanding anticancer effect in vitro and in vivo, suggesting that CDK7 is a potential therapeutic target for gastric cancer patients.

PMID: 30662617 [PubMed]

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