Figure 5.

Statin therapy for cancer. When statins enter cells and block HMG-CoA reductase activity, the mevalonate pathway end product, RhoA is depleted. Depression of RhoA can affect the stability of the cytoskeleton, further prevent the YAP entering cell nucleus, here, YAP will drive transcription of target genes with TEAD to promote the tumor tissue growth. At the same time, KRAS is another important downstream molecule in the mevalonate pathway, which can activate the MAPK signal to accelerate cell proliferation, thus restraining KRAS will delay cancer cell proliferation. In addition to the mevalonate pathway, statins could directly depress the AKT signal, effect the synthesis and degradation p21 and p27, at last block the cell cycle progression. Besides, statin can activate caspase-8, caspase-3 and caspase-9 to induce apoptosis, and suppress angiogenesis by inhibiting TNF-α.