Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
China State Key Laboratory of New Drug & Pharmaceutical Process, Center for Pharmacological Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, 1111 Rd. Zhongshanbeiyi, Hongkou, Shanghai, 200437, China.
BMC Cancer. 2020 Sep 29;20(1):936. doi: 10.1186/s12885-020-07447-3.
Hepatocellular carcinoma (HCC) is a common malignant tumor with characteristics of poor prognosis, high morbidity and mortality worldwide. In particular, only a few systemic treatment options are available for advanced HCC patients, and include sorafenib and the recently described atezolizumab plus bevacizumab regimen as possible first-line treatments. We here propose acteoside, a phenylethanoid glycoside widely distributed in many medicinal plants as a potential candidate against advanced HCC.
Cell proliferation, colony formation and migration were analyzed in the three human HCC cell lines BEL7404, HLF and JHH-7. Angiogenesis assay was performed using HUVESs. The BEL7404 or JHH-7 xenograft nude mice model was established to analyze the possible antitumor effects of acteoside. qRT-PCR and western blotting were used to reveal the potential antitumor mechanisms of acteoside.
Acteoside inhibited cell proliferation, colony formation and migration in all the three human HCC cell lines BEL7404, HLF and JHH-7. The prohibition of angiogenesis by acteoside was revealed by the inhibition of tube formation and cell migration of HUVECs. The combination of acteoside and sorafenib produced stronger inhibition of cell colony formation and migration of the HCC cells as well as of angiogenesis of HUVECs. The in vivo antitumor efficacy of acteoside was further demonstrated in BEL7404 or JHH-7 xenograft nude mice model, with an enhancement when combined with sorafenib in inhibiting the growth of JHH-7 xenograft. Further treatment of JHH-7 cells with acteoside revealed an increase in the level of tumor suppressor protein p53 as well as a decrease of kallikrein-related peptidase (KLK1, 2, 4, 9 and 10) gene level with no significant changes of the rest of KLK1-15 genes.
Acteoside exerts an antitumor effect possibly through its up-regulation of p53 levels as well as inhibition of KLK expression and angiogenesis. Acteoside could be useful as an adjunct in the treatment of advanced HCC in the clinic.
肝细胞癌（HCC）是一种常见的恶性肿瘤，具有全球预后差、发病率和死亡率高的特点。特别是，晚期 HCC 患者仅有少数系统治疗选择，包括索拉非尼和最近描述的阿替利珠单抗联合贝伐珠单抗方案作为可能的一线治疗。我们在此提出，毛蕊花糖苷，一种广泛存在于许多药用植物中的苯乙醇苷，作为一种治疗晚期 HCC 的潜在候选药物。
在三种人 HCC 细胞系 BEL7404、HLF 和 JHH-7 中分析细胞增殖、集落形成和迁移。使用 HUVESs 进行血管生成测定。建立 BEL7404 或 JHH-7 异种移植裸鼠模型，分析毛蕊花糖苷的可能抗肿瘤作用。使用 qRT-PCR 和 Western blot 揭示毛蕊花糖苷的潜在抗肿瘤机制。
毛蕊花糖苷抑制三种人 HCC 细胞系 BEL7404、HLF 和 JHH-7 的细胞增殖、集落形成和迁移。毛蕊花糖苷抑制管形成和 HUVEC 细胞迁移，显示其抑制血管生成的作用。毛蕊花糖苷与索拉非尼联合使用对 HCC 细胞集落形成和迁移以及 HUVEC 血管生成的抑制作用更强。毛蕊花糖苷在 BEL7404 或 JHH-7 异种移植裸鼠模型中的体内抗肿瘤疗效进一步得到证实，与索拉非尼联合使用时可增强 JHH-7 异种移植的生长抑制作用。进一步用毛蕊花糖苷处理 JHH-7 细胞，发现肿瘤抑制蛋白 p53 水平升高，激肽释放酶相关肽（KLK1、2、4、9 和 10）基因水平降低，其余 KLK1-15 基因无明显变化。
毛蕊花糖苷通过上调 p53 水平以及抑制 KLK 表达和血管生成发挥抗肿瘤作用。毛蕊花糖苷可作为晚期 HCC 临床治疗的辅助药物。
