RIPK1 and osteosarcoma: It was suggested that shikonin might increase the expression level of RIPK1 in shikonin-treated glioma cells and the expression level of RIPK1/RIPK3 in shikonin-treated osteosarcoma cells and pancreatic cancer cells, which resulted in the initiation of necroptosis and could be rescued by NEC1 (141, 142, 144) What’s more, it has been reported that the anti-cancer drug resistance of drug-sensitive cancer cell lines, including MCF-7 and HEK293, can be overcome, and these cells show the typical morphologic characteristics of necroptosis when treated with shikonin (44).