8u, a pro-apoptosis/cell cycle arrest compound, suppresses invasion and metastasis through HSP90α downregulating and PI3K/Akt inactivation in hepatocellular carcinoma cells

摘要

8u, an acridine derivative, has been proved effective anti-hepatocarcinoma effect, while the underlying mechanism remains unclear. Here, metabolomics and proteomics approaches were applied to study its anti-cancer mechanism and explore its effect on HepG2 cells’ invasion and metastasis abilities. The results showed that 8u significantly suppressed HepG2 cells migration and enhanced cell-to-cell junctions. The inhibition effect of 8u on invasion and metastasis disappeared after HSP90α gene silencing, and was reversed after HSP90α overexpression. The biological experimental results indicated that 8u also blocked PI3K/Akt pathway, thereby reducing fatty acid synthase (FASN) protein expression and disordering intracellular lipid metabolism to inhibit cell invasion and metastasis. In addition, HSP90α protein and PI3K/Akt pathway could co-adjust to each other. These findings demonstrated that 8u could efficiently suppress the invasion and metastasis of HepG2 cells by decreasing the expression of HSP90α protein and inhibiting the PI3K/Akt signaling pathway, which could be used as a potential candidate for the treatment of HCC.