Effect of Hsp90 Inhibitor KW-2478 on HepG2 Cells

Abstract

Objective: The objectives of this study were to investigate the effects of proliferation, apoptosis, cell cycle, invasion, and senescence of KW-2478 on HepG2 cells, and to explore the related mechanism of apoptosis and the cell cycle.

Methods: HepG2 cells (hepatocellular carcinoma cells) were cultured with KW-2478, at different doses and for different times, in vitro. The MTT assay was used to detect the effect of KW-2478 on proliferation of HepG2 cells. Flow cytometry was used to determine the effects of KW-2478 on the cell cycle and apoptosis of HepG2 cells. The Transwell assay was used to determine the effect of KW-2478 on cell invasion. The β-galactosidase assay tested the effect of low-dose KW-2478 on the senescence of HepG2 cells. Western blotting and the quantitative polymerase chain reaction were used respectively to assess changes in protein and mRNA levels of related factors in HepG2 cells after the KW-2478 treatment.

Results: KW-2478 significantly inhibited proliferation of HepG2 cells. KW-2478 induced apoptosis and cell cycle arrest of HepG2 cells, and inhibited the invasion of HepG2 cells; low dose KW-2478 promoted HepG2 senescence.

Conclusion: KW-2478 inhibited the proliferation of HepG2 cells, induced apoptosis and cell cycle arrest, inhibited invasion, and promoted senescence. KW-2478 affected the expression of related factors in the mitochondrial apoptotic signaling and cell cycle-related regulatory pathways. KW-2478 downregulated the expression of STAT3, which is a key factor in the JAK-STAT pathway, indicating that KW-2478 may affect the function of HepG2 cells by downregulating STAT3.

Keywords: HepG2; KW-2478; apoptosis; cell cycle; invasion; proliferation; senescence..