Tsai Jai-Jen, Hsu Fei-Ting, Pan Po-Jung, Chen Chia-Wen, Kuo Yu-Cheng
Division of Gastroenterology, Department of Medicine, National Yang-Ming University Hospital, I-Lan, Taiwan, R.O.C.
Cancer Medical Care Center, National Yang Ming University Hospital, I-Lan, Taiwan, R.O.C.
Anticancer Res. 2018 Apr;38(4):2119-2125. doi: 10.21873/anticanres.12452.
BACKGROUND/AIM: In a previous study, we showed that amentoflavone promotes sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro. However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC in vivo is unknown. The aim of the present study was to verify the anticancer effect of amentoflavone combined with sorafenib in HCC in vivo.
HCC SK-Hep1 tumor-bearing mice were treated with vehicle, sorafenib, amentoflavone, or combination for 14 days, respectively. Effect of sorafenib, amentoflavone, or their combination on tumor growth, anti-apoptotic potential, apoptotic signaling and general toxicity were evaluated with digital caliper, immunohistochemistry staining and body weight.
Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways.
Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti-apoptotic potential and induction of apoptosis in HCC in vivo.
背景/目的：在之前的一项研究中，我们发现穗花杉双黄酮在体外可促进索拉非尼诱导的肝癌（HCC）细胞凋亡。然而，穗花杉双黄酮在体内是否能增强索拉非尼对HCC的抗癌疗效尚不清楚。本研究的目的是验证穗花杉双黄酮联合索拉非尼在体内对HCC的抗癌作用。
将荷HCC SK-Hep1肿瘤的小鼠分别用赋形剂、索拉非尼、穗花杉双黄酮或联合用药进行处理，为期14天。用数字卡尺、免疫组化染色和体重评估索拉非尼、穗花杉双黄酮或它们的组合对肿瘤生长、抗凋亡潜力、凋亡信号传导和一般毒性的影响。
我们的结果表明，与单药治疗相比，穗花杉双黄酮显著增强了索拉非尼抑制的肿瘤生长以及ERK/AKT磷酸化和抗凋亡蛋白的表达。此外，穗花杉双黄酮还通过外源性和内源性凋亡途径触发索拉非尼诱导的细胞凋亡。
穗花杉双黄酮通过阻断抗凋亡潜力和诱导体内HCC细胞凋亡来提高索拉非尼的治疗效果。
