alloin and Liver-Neoplasms

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.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Autophagy; Carcinoma, Hepatocellular; Drug Synergism; Emodin; Female; Hep G2 Cells; Humans; Liver Neoplasms; Metformin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Xenograft Model Antitumor Assays