Rigosertib and Cholangiocarcinoma: A Cell Cycle Affair

International Journal of Molecular Sciences

Mariarosaria Miloso¹  Alessio Malacrida¹  Guido Cavaletti¹ 

[1] Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, MB, Italy;

关键词: Rigosertib;    PLK1 inhibitor;    cholangiocarcinoma;    EGI-1 cells;    cell cycle;    p53;   

DOI  :  10.3390/ijms23010213

来源: DOAJ

【 摘 要 】

Rigosertib is multi-kinase inhibitor that could represent an interesting therapeutic option for non-resectable patients with cholangiocarcinoma, a very aggressive hepatic cancer with limited effective treatments. The Western blotting technique was used to evaluate alterations in the expression of proteins involved in the regulation of the cell cycle of cholangiocarcinoma EGI-1 cells. Our results show an increase in EMI1 and Cyclin B protein levels after Rigosertib treatment. Moreover, the phosphorylation of CDK1 is significantly reduced by Rigosertib, while PLK1 expression increased after 24 h of treatment and decreased after 48 h. Finally, we evaluated the role of p53. Its levels increase after Rig treatment, and, as shown in the cell viability experiment with the p53 inhibitor Pifithrin, its activity is necessary for the effects of Rigosertib against the cell viability of EGI-1 cells. In conclusion, we hypothesized the mechanism of the action of Rigosertib against cholangiocarcinoma EGI-1 cells, highlighting the importance of proteins involved in the regulation of cell cycles. The CDK1-Cyclin B complex and p53 play an important role, explaining the Block in the G2/M phase of the cell cycle and the effect on cell viability

【 授权许可】

Unknown