HIF1A and liver cancer: But there are also studies that shikonin can also activate PKM2 bypass such as PKM2/NRF2/Bcl2-associated athanogene 3 pathway and PKM2/HIF-1α pathway and further reducing tumor cell apoptosis, increasing glycolysis, making liver cancer cells resistant to its anti-liver cancer effect,[3,43] suggesting that shikonin inhibits one of PKM2’s non-metabolic enzyme pathways, may cause other pathways activation, combined with related pathway inhibitors may enhance its anti-liver cancer effect.