Jing Ji, Zhen Zhang, Guanrong Li, Lingyi Zuo, JIAO-JIAO Zhou, Xiu-jun Wang, SHAO-JIE Ma, Bin Liu, JIN-QING Han, Xiao Hou
{"title":"新型 CDK4/6 抑制剂 WXJ-8 通过细胞周期对乳腺癌发挥抗癌作用","authors":"Jing Ji, Zhen Zhang, Guanrong Li, Lingyi Zuo, JIAO-JIAO Zhou, Xiu-jun Wang, SHAO-JIE Ma, Bin Liu, JIN-QING Han, Xiao Hou","doi":"10.32383/appdr/173986","DOIUrl":null,"url":null,"abstract":"The novel Abemaciclib derivative WXJ-8 may be a promising anti-tumour drug; however, its mechanism of action and clinical value need to be further verified in research. Cell cycle regulating systems are critical in parthenogenesis and progression. Because of its involvement in regulating cell cycle checkpoints, the CDK4/6-CyclinD1-Rb-E2F1 signalling pathway has been proposed as a possible therapeutic target for breast cancer. As a result, WXJ-8, a new and highly specific CDK4/6 inhibitor, was developed and synthesized in this investigation. The activity of WXJ-8 against breast cancer cells in vitro was detected by MTT method. The main subjects were MDA-MB-231 and MCF-7 cells. Plate cloning, wound healing, invasion and adhesion experiments revealed that WXJ-8 had strong anti-proliferation, migration, invasion, and adhesion effects on breast cancer cells. Protein blotting revealed significant down regulation of CDK4, CDK6, p-Rb, E2F1 and other cell cycle factors in the CDK4/6-CyclinD1-Rb-E2F1 pathway, as well as activation of Bcl-2, Caspase-3, and Cleaved Caspase-3 apoptotic factor expression, resulting in MDA-MB-231 cell cycle arrest and apoptosis. Finally, our research implies that WXJ-8 might be a potential anti-triple-negative breast cancer medication candidate.","PeriodicalId":7135,"journal":{"name":"Acta Poloniae Pharmaceutica - Drug Research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel CDK4/6 lnhibitor, WXJ-8 -Exerts Anti-effects Through Cell Cycle in Breast Cancer\",\"authors\":\"Jing Ji, Zhen Zhang, Guanrong Li, Lingyi Zuo, JIAO-JIAO Zhou, Xiu-jun Wang, SHAO-JIE Ma, Bin Liu, JIN-QING Han, Xiao Hou\",\"doi\":\"10.32383/appdr/173986\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The novel Abemaciclib derivative WXJ-8 may be a promising anti-tumour drug; however, its mechanism of action and clinical value need to be further verified in research. Cell cycle regulating systems are critical in parthenogenesis and progression. Because of its involvement in regulating cell cycle checkpoints, the CDK4/6-CyclinD1-Rb-E2F1 signalling pathway has been proposed as a possible therapeutic target for breast cancer. As a result, WXJ-8, a new and highly specific CDK4/6 inhibitor, was developed and synthesized in this investigation. The activity of WXJ-8 against breast cancer cells in vitro was detected by MTT method. The main subjects were MDA-MB-231 and MCF-7 cells. Plate cloning, wound healing, invasion and adhesion experiments revealed that WXJ-8 had strong anti-proliferation, migration, invasion, and adhesion effects on breast cancer cells. Protein blotting revealed significant down regulation of CDK4, CDK6, p-Rb, E2F1 and other cell cycle factors in the CDK4/6-CyclinD1-Rb-E2F1 pathway, as well as activation of Bcl-2, Caspase-3, and Cleaved Caspase-3 apoptotic factor expression, resulting in MDA-MB-231 cell cycle arrest and apoptosis. Finally, our research implies that WXJ-8 might be a potential anti-triple-negative breast cancer medication candidate.\",\"PeriodicalId\":7135,\"journal\":{\"name\":\"Acta Poloniae Pharmaceutica - Drug Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-11-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Poloniae Pharmaceutica - Drug Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.32383/appdr/173986\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Poloniae Pharmaceutica - Drug Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.32383/appdr/173986","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Novel CDK4/6 lnhibitor, WXJ-8 -Exerts Anti-effects Through Cell Cycle in Breast Cancer
The novel Abemaciclib derivative WXJ-8 may be a promising anti-tumour drug; however, its mechanism of action and clinical value need to be further verified in research. Cell cycle regulating systems are critical in parthenogenesis and progression. Because of its involvement in regulating cell cycle checkpoints, the CDK4/6-CyclinD1-Rb-E2F1 signalling pathway has been proposed as a possible therapeutic target for breast cancer. As a result, WXJ-8, a new and highly specific CDK4/6 inhibitor, was developed and synthesized in this investigation. The activity of WXJ-8 against breast cancer cells in vitro was detected by MTT method. The main subjects were MDA-MB-231 and MCF-7 cells. Plate cloning, wound healing, invasion and adhesion experiments revealed that WXJ-8 had strong anti-proliferation, migration, invasion, and adhesion effects on breast cancer cells. Protein blotting revealed significant down regulation of CDK4, CDK6, p-Rb, E2F1 and other cell cycle factors in the CDK4/6-CyclinD1-Rb-E2F1 pathway, as well as activation of Bcl-2, Caspase-3, and Cleaved Caspase-3 apoptotic factor expression, resulting in MDA-MB-231 cell cycle arrest and apoptosis. Finally, our research implies that WXJ-8 might be a potential anti-triple-negative breast cancer medication candidate.