Background:
Cancer is the second leading cause of death globally. However, most of the new anti-
cancer agents screened by traditional
drug screening methods fail in the clinic because of lack of efficacy. Choosing an appropriate in vitro
tumor model is crucial for preclinical
drug screening. In this study, we screened anti-hepatocarcinoma (HCC) drugs using a novel spheroid cell culture device. Methods: Four HCC cell lines were three-dimensionally (3D) cultured to screen 19 small molecular agents. 3D-cultured primary HCC cells and a
tumor-bearing mouse model were used to verify the candidate anti-hepatocarcinoma agent. Cell function experiments and western blotting were conducted to explore the anti-hepatocarcinoma mechanism of the candidate agent. Results: We found that
CUDC-907 can serve as a potent anti-hepatocarcinoma agent. The study data show that
CUDC-907 (
fimepinostat), a novel dual acting inhibitor of
phosphoinositide 3-kinase (PI3K) and
histone deacetylase (HDAC), has potent inhibitory effects on HCC cell lines and primary HCC cells in vitro, Animal studies have shown that
CUDC-907 can also suppress HCC cells in vivo. Furthermore, we found that
CUDC-907 inhibits the PI3K/AKT/mTOR pathway and downregulates the expression of c-Myc, leading to the suppression of HCC cells. Conclusion: Our results suggest that
CUDC-907 can be a candidate anti-HCC
drug, and the 3D in vitro
drug screening method based on our novel spheroid culture device is promising for future
drug screening efforts.