Fig. 6.

The mechanism of the PB2 effect on glycolysis inhibition in HCC cells. PKM2 is the last rate-limiting enzyme during glycolysis. The cytoplasmic HSP90 bound PKM2 to maintain the stability of PKM2. While PKM2 also translocated into the nucleus and interacted with HIF-1α to promote the transcription of HIF-1α targeted genes, such as the key glycolytic enzymes (including PKM2), the glucose and lactate transporters, c-Myc, Bcl-xL, and VEGF. In our study, we found that PB2 inhibited the expression and nuclear translocation of PKM2, therefore it disrupted the interaction between PKM2/HSP90/HIF-1α, to suppress aerobic glycolysis, proliferation, and to trigger apoptosis via HIF-1α-mediated transcription suppression in HCC