Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan.
Sci Rep. 2019 Jul 17;9(1):10338. doi: 10.1038/s41598-019-46891-5.
Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), a leading cause of cancer mortality worldwide. Hepatitis B X protein (HBx) and pre-S2 mutant have been proposed as the two most important HBV oncoproteins that play key roles in HCC pathogenesis. Curcumin is a botanical constituent displaying potent anti-inflammatory and anti-cancer properties without toxic side effects. Phytosomal formulation of curcumin has been shown to exhibit enhanced bioavailability, improved pharmacokinetics, and excellent efficacy against many human diseases. However, effectiveness of phytosomal curcumin for HCC treatment remains to be clarified. In this study, we evaluated chemopreventive effect of phytosomal curcumin on HBV-related HCC by using a transgenic mouse model specifically expressing both HBx and pre-S2 mutant in liver. Compared with unformulated curcumin, phytosomal curcumin exhibited significantly greater effects on suppression of HCC formation, improvement of liver histopathology, decrease of lipid accumulation and leukocyte infiltration, and reduction of total tumor volume in transgenic mice. Moreover, phytosomal curcumin exerted considerably stronger effects on activation of anti-inflammatory PPARγ as well as inhibition of pro-inflammatory NF-κB than unformulated curcumin. Furthermore, phytosomal curcumin showed a comparable effect on suppression of oncogenic mTOR activation to unformulated curcumin. Our data demonstrated that phytosomal curcumin has promise for HCC chemoprevention in patients with chronic HBV infection.
慢性乙型肝炎病毒（HBV）感染是肝细胞癌（HCC）发展的主要危险因素，HCC 是全球癌症死亡的主要原因。乙型肝炎 X 蛋白（HBx）和前 S2 突变体被认为是两种最重要的 HBV 致癌蛋白，它们在 HCC 的发病机制中发挥关键作用。姜黄素是一种植物成分，具有强大的抗炎和抗癌特性，没有毒副作用。姜黄素的植物皂素制剂已被证明具有增强的生物利用度、改善的药代动力学和对许多人类疾病的优异疗效。然而，植物皂素姜黄素对 HCC 治疗的有效性仍需阐明。在这项研究中，我们使用在肝脏中特异性表达 HBx 和前 S2 突变体的转基因小鼠模型，评估了植物皂素姜黄素对 HBV 相关 HCC 的化学预防作用。与未形成姜黄素相比，植物皂素姜黄素对抑制 HCC 形成、改善肝组织病理学、减少脂质积累和白细胞浸润以及减少转基因小鼠的总肿瘤体积具有显著更大的作用。此外，植物皂素姜黄素对抗炎性 PPARγ的激活以及对促炎性 NF-κB 的抑制作用明显强于未形成姜黄素。此外，植物皂素姜黄素对抑制致癌 mTOR 激活的作用与未形成姜黄素相当。我们的数据表明，植物皂素姜黄素有望用于慢性 HBV 感染患者的 HCC 化学预防。
