<br>芦荟苷与二甲双胍联合通过PI3K/AKT/mTOR通路抑制肝细胞癌的生长和侵袭、诱导细胞凋亡和自噬，从而增强抗肿瘤作用。,Cancer Medicine

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芦荟苷与二甲双胍联合通过PI3K/AKT/mTOR通路抑制肝细胞癌的生长和侵袭、诱导细胞凋亡和自噬，从而增强抗肿瘤作用。
Cancer Medicine ( IF 2.9 ) Pub Date : 2019-12-12 , DOI: 10.1002/cam4.2723
Ruijie Sun ₁ , Ruiren Zhai ₂ , Changlin Ma ₁ , Wei Miao ₃

Affiliation

肝细胞癌（HCC）是世界范围内一种毁灭性且高度转移的癌症。二甲双胍（MET）是治疗2型糖尿病的优先药物；然而，它具有多种生物效应，如抗癌和保肝活性。在此，我们在体外和体内检查了芦荟素 (barbaloin) 和 MET 以及联合治疗对 HCC 细胞系的影响。结果，芦荟素和MET单独对HepG2和Bel-7402细胞的增殖和侵袭表现出抑制作用。特别是，芦荟苷和 MET 联合治疗在体外显示出增强的抑制作用。芦荟素和 MET 单独在体外诱导细胞凋亡和自噬。同样，芦荟素和 MET 协同促进 HepG2 和 Bel-7402 细胞的凋亡和自噬。在 HepG2 异种移植模型中，芦荟素与 MET 结合可限制肿瘤生长并促进细胞凋亡和自噬。体外和体内结果均表明芦荟素和 MET 单独治疗以及联合治疗均激活 PI3K/AKT/mTOR 通路。总体而言，我们的研究表明芦荟素和 MET 联合治疗通过 PI3K/AKT/mTOR 通路抑制 HCC 的生长和侵袭以及诱导细胞凋亡和自噬，从而增强抗肿瘤作用。

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Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway.

Hepatocellular carcinoma (HCC) is a devastating and highly metastatic cancer worldwide. Metformin (MET) is the priority drug for treatment of type 2 diabetes; however, it possesses multiple biological effects like anticancer and hepatoprotective activity. Herein, we examined the effects of aloin (barbaloin) and MET as well as combination treatment in HCC cell line in vitro and in vivo. As a result, aloin and MET alone exhibited inhibitory effects on proliferation and invasion of HepG2 and Bel-7402 cells. Specially, combination treatment of aloin and MET showed enhanced inhibitory effects in vitro. Aloin and MET alone induced apoptosis and autophagy in vitro. Similarly, aloin and MET cooperated to promote apoptosis and autophagy in HepG2 and Bel-7402 cells. In the HepG2 xenograft models, aloin in combination with MET confine tumor growth and facilitate apoptosis and autophagy. Both the in vitro and in vivo results showed that aloin and MET alone as well as combination treatment activated the PI3K/AKT/mTOR pathway. Overall, our research demonstrated that the concomitant treatment with aloin and MET enhances the antitumor effect by inhibiting the growth and invasion as well as inducing apoptosis and autophagy in HCC through PI3K/AKT/mTOR pathway.

更新日期：2019-12-13

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