title: Selective CDK7 inhibition with BS-181 suppresses cell proliferation and induces cell cycle arrest and apoptosis in gastric cancer.
abstract: Cyclin-dependent kinase (CDK) family members have been considered as attractive therapeutic targets for cancer. In this study, we aim to investigate the anticancer effects of a selective CDK7 inhibitor, BS-181, in gastric cancer (GC) cell line. Human GC cells (BGC823) were cultured with or without BS-181 at different concentrations for 24-72 hours. BS-181 significantly reduced the activity of CDK7 with downregulation of cyclin D1 and XIAP in GC cells. Treatment with BS-181 induced cell cycle arrest and apoptosis. The expression of Bax and caspase-3 was significantly increased, while Bcl-2 expression was decreased in cells treated with BS-181. In addition, the inhibition of CDK7 with BS-181 resulted in reduced rates of proliferation, migration, and invasion of gastric cells. Those results demonstrated the anticancer activities of selective CDK7 inhibitor BS-181 in BGC823 cells, suggesting that CDK7 may serve as a novel therapeutic target or the treatment of GC.
authors.affiliation: Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Bo-Yong
authors.initials: BY
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Quan-Yan
authors.initials: QY
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Zhi-Su
authors.initials: ZS
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C000592924:BS-181; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase
keywords: BS-181; anticancer activities; gastric cancer; selective CDK7 inhibitor