INS and colorectal carcinoma: In addition, metformin downregulated the mevalonate pathway as myeloid-derived suppressor cells and M2 macrophages in CRC mouse models [183] sensitized CRC cells to 5-Fluorouracil (5-FU) and irinotecan [184] and counteracted insulin-induced oxaliplatin resistance in HCT116 and LoVo cells via AMPK activation [97].