RT Journal Article
SR Electronic
T1 Inactivation of AKT/ERK Signaling and Induction of Apoptosis Are Associated With Amentoflavone Sensitization of Hepatocellular Carcinoma to Lenvatinib
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2495
OP 2505
DO 10.21873/anticanres.15728
VO 42
IS 5
A1 CHE-JUI YANG
A1 MENG-HSUAN WU
A1 JAI-JEN TSAI
A1 FEI-TING HSU
A1 TE-CHUN HSIA
A1 KUO-CHING LIU
A1 YU-CHENG KUO
YR 2022
UL http://ar.iiarjournals.org/content/42/5/2495.abstract
AB Background/Aim: AKT/ERK signaling transduction and anti-apoptosis effects have both been recognized as important mediators of hepatocellular carcinoma (HCC) progression. Targeting AKT/ERK signaling and mediating apoptosis may be beneficial for alleviating HCC growth. Lenvatinib, a tyrosine kinase inhibitor, has been approved by the FDA to treat HCC since 2018 as a monotherapy with limited efficacy. Amentoflavone, a biflavonoid in natural plants, has been shown to have the potential to suppress HCC progression in previous studies. Whether the combination of lenvatinib and amentoflavone may show superior HCC suppression is unclear. Materials and Methods: We used MTT, flow cytometry and western blotting assays to identify the role of lenvatinib and amentoflavone in both Hep3B and Huh7 cells. Results: We found that amentoflavone enhances the suppressive effect of AKT/ERK signaling induced by lenvatinib and, thus, sensitizes HCC to lenvatinib. The intrinsic/extrinsic apoptosis pathways induced by lenvatinib were also boosted by amentoflavone. Conclusion: Amentoflavone sensitization of HCC to lenvatinib is associated with AKT/ERK inactivation and apoptosis induction.