Inhibition of the CDK4/6-Cyclin D-Rb Pathway by Ribociclib Augments Chemotherapy and Immunotherapy in Renal Cell Carcinoma
Ribociclib significantly enhances the in vitro efficacy of chemotherapy and immunotherapy in sensitive but not resistant RCC cell lines. Combination of ribociclib with 5-FU (chemotherapeutic agent) or IFN-α (immunotherapeutic agent) is significantly more effective in inhibiting proliferation (a) and inducing apoptosis (b) than 5-FU or IFN-α alone in sensitive but not resistant cell lines. Results shown in (a) are relative to control (value set as 1). 5-FU at 1 μM and IFN-α at 100 IU/ml were used in the combination assays in all tested RCC cell lines. Ribociclib at 0.1 μM in 786-O, CaKi-2, SW839, and UM-RC-2 cell lines, at 0.2 μM in 769-P, A-704, and ACHN, and at 0.8 μM in CaKi-1 and A498 cell lines was used for the proliferation assay. Ribociclib at 0.8 μM in 786-O, CaKi-2, SW839, and UM-RC-2 cell lines and at 1.6 μM in 769-P, A-704, ACHN, CaKi-1, and A498 cell lines was used for the apoptosis assay. , compared to 5-FU or IFN-α alone.
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