Combination simvastatin and metformin induces G1-phase cell cycle arrest and Ripk1- and Ripk3-dependent necrosis in C4-2B osseous metastatic castration-resistant prostate cancer cells.

In siScramble- or siRipk3-transfected C4-2B cells, Nec-1 and Ripk3 knockdown each partially rescued C4-2B viability by 18−23% and 11−17%, respectively ( Figure 8a ); yet, when Ripk3 protein expression and Ripk1 activity were simultaneously inhibited, it resulted in highly significant 36−42% rescue of C4-2B cell viability from the effect of SIM+MET treatment for 72 h.

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