Anti-hepatocellular carcinoma activity of the cyclin-dependent kinase inhibitor AT7519
Kaja Karaś, Iwona Karwaciak, Katarzyna Chałaśkiewicz, Anna Sałkowska, Joanna Pastwińska, Rafał A. Bachorz, Marcin Ratajewski
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancerous tumors and one of the leading causes of death among cancer-related disorders. Chemotherapy is ineffective in HCC patients, and the number of drugs that are in use is limited. Thus, new molecules are needed that could increase the effectiveness of anti-HCC regimens. Here, we show that AT7519, a CDK inhibitor, exerts positive effects on HCC cells: it inhibits proliferation, migration and clonogenicity. Detailed analysis of the transcriptomes of cells treated with this compound indicated that AT7519 affects a substantial portion of genes that are associated with HCC development and progression. Moreover, we showed that the concomitant use of AT7519 with gefitinib or cabozantinib sensitized HCC cells to these drugs. Thus, our research indicates that AT7519 is worth considering in monotherapy for hepatocellular carcinoma patients or in combination with other drugs, e.g., gefitinib or cabozantinib.