Aim

Hepatocellular carcinoma (HCC) is a potentially life-threatening cancer. In the current study, anti-HCC efficacy of amygdalin, or metformin alone or in combination in comparison to doxorubicin was studied.

Main methods

Both in-vitro and in-vivo based models. HepG-2 and Huh-7 cell lines as established in-vitro model for HCC were treated with different concentrations of indicated drugs to evaluate the cytotoxicity and determine IC₅₀ for 24, 48 and 72 h. Moreover, the effect of different treatments on apoptosis and cell cycle using flow cytometric analysis were studied. Hepatocellular carcinoma induced in rats by diethyl-nitrosamine and carbon tetrachloride was established, to further investigate the efficacy of indicated drugs. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were measured by spectrophotometer, alpha-fetoprotein, cytochrome-c, caspase-3 and malondialdehyde were measured by ELISA, and liver biopsies were also evaluated histopathologically.

Key findings

In-vitro results showed that the combination has a promising effect when compared to amygdalin or metformin alone as it is more cytotoxic and have higher ability for induction of apoptosis and arresting cell cycle. In-vivo doxorubicin has a good effect for treating HCC. Also, the combination showed a promising prognostic effect depending on the cytotoxic activity and tumor marker when compared to amygdalin or metformin alone.

Significance

Based on the current data, it was hypothesized that amygdalin and metformin especially when used in combination will be a promising approach with low side effects for enhancement of HCC.

中文翻译：

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苦杏仁苷、二甲双胍和两者联合对抗阿霉素治疗肝细胞癌的体外和体内研究

目的

肝细胞癌 (HCC) 是一种可能危及生命的癌症。在当前的研究中，研究了苦杏仁苷或二甲双胍单独或联合使用与阿霉素相比的抗 HCC 功效。

主要方法

基于体外和体内的模型。用不同浓度的指定药物处理作为建立的 HCC 体外模型的 HepG-2 和 Huh-7 细胞系，以评估细胞毒性并确定24、48 和 72 小时的IC ₅₀。此外，使用流式细胞术分析研究了不同处理对细胞凋亡和细胞周期的影响。建立了二乙基亚硝胺和四氯化碳在大鼠中诱导的肝细胞癌，以进一步研究指定药物的疗效。天冬氨酸氨基转移酶、丙氨酸氨基转移酶和碱性磷酸酶通过分光光度计测量，甲胎蛋白、细胞色素-c、caspase-3和丙二醛通过ELISA测量，肝脏活检也通过组织病理学进行评估。

主要发现

体外结果表明，与单独使用苦杏仁苷或二甲双胍相比，该组合具有良好的效果，因为它具有更强的细胞毒性，并且具有更高的诱导细胞凋亡和阻止细胞周期的能力。体内阿霉素治疗HCC有很好的效果。此外，与单独的苦杏仁苷或二甲双胍相比，该组合显示出有希望的预后效果，这取决于细胞毒活性和肿瘤标志物。

意义

根据目前的数据，假设苦杏仁苷和二甲双胍，尤其是联合使用时，将是一种有前景的方法，具有低副作用，可用于增强 HCC。