Division of Urology, Department of Surgery, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
Department of Emergency Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
Anticancer Res. 2022 May;42(5):2495-2505. doi: 10.21873/anticanres.15728.
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.
We used MTT, flow cytometry and western blotting assays to identify the role of lenvatinib and amentoflavone in both Hep3B and Huh7 cells.
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.
Amentoflavone sensitization of HCC to lenvatinib is associated with AKT/ERK inactivation and apoptosis induction.
背景/目的：AKT/ERK 信号转导和抗细胞凋亡作用已被认为是肝癌（HCC）进展的重要介质。靶向 AKT/ERK 信号并介导细胞凋亡可能有助于缓解 HCC 生长。自 2018 年以来，FDA 已批准仑伐替尼作为单一药物治疗 HCC，但其疗效有限。amentoflavone 是一种天然植物中的双黄酮类化合物，之前的研究表明它具有抑制 HCC 进展的潜力。仑伐替尼和 amentoflavone 的联合使用是否可能具有更好的 HCC 抑制作用尚不清楚。
我们使用 MTT、流式细胞术和 Western blot 检测来确定 lenvatinib 和 amentoflavone 在 Hep3B 和 Huh7 细胞中的作用。
我们发现 amentoflavone 增强了 lenvatinib 诱导的 AKT/ERK 信号的抑制作用，从而使 HCC 对 lenvatinib 敏感。amentoflavone 还增强了 lenvatinib 诱导的内在/外在细胞凋亡途径。
amentoflavone 使 HCC 对 lenvatinib 的敏感性与 AKT/ERK 失活和细胞凋亡诱导有关。
