The combined inhibiting effect and related mechanism of Curcumin and ABT-737 on epithelial-mesenchymal transition of human liver cancer cell

Abstract

Abstract: Objective To explore the combined inhibiting effect and related mechanism of Curcumin and ABT-737 on epithelial-mesenchymal transition (EMT) of human liver cancer cell.Methods After treatment with 2 μmol/L Curcumin, 5 μmol/L ABT-737 alone or 2 μmol/L Curcumin in combination with 5 μmol/L ABT-737, the morphological change of 7404 cells was observed under an inverted microscope, the cell migration was analyzed by Wound Healing, the expression levels of Vimentin, N-cadherin, ZEB1 and E-cadherin proteins in 7404 cells were detected by Western blotting. The expression levels of p-beta-catenin, p-JNK, Snail and Twist proteins in 7404 cells were also detected by Western blotting. The animal models of liver cancer(Alb-Cre; P53^f/f; Ras)was established. The numbers of metastatic tumor in liver was observed and calculated under hematoxylin eosin stain.Results As compared with the 7404 cells with treatment of 2 μmol/L Curcumin or 5 μmol/L ABT-737, the numbers of 7404 cells that changed shape to spindle-like after treatment with 2 μmol/L Curcumin + 5 μmol/L ABT-737 were obviously reduced (P<0.05), with significantly decline of cell migration ability. Compared with the 2 μmol/L Curcumin or 5 μmol/L ABT-737 group, the expression levels of E-cadherin protein were significantly increased while the expression levels of Vimentin, N-cadherin and ZEB1 protein were significantly decreased in 7404 cells after treatment with 2 μmol/L Curcumin and 5 μmol/L ABT-737 (P<0.05). What’s more, as compared with the 7404 cells treated with the 2 μmol/L Curcumin or 5 μmol/L ABT-737 group,the expression levels of p-beta-catenin and p-JNK protein were significantly increased while the expression levels of Snail and Twist protein were decreased significantly in the 7404 cells after treatment with 2 μmol/L Curcumin + 5 μmol/L ABT-737 (P<0.05). The numbers of metastatic tumor in liver were decreased significantly in the animal models of liver cancer (Alb-Cre; P53^f/f; Ras) after Curcumin and ABT-737 treatment than those in the animal models without any treatment (as a control) (P<0.05).Conclusion The combination treatment of curcumin and ABT-737 may inhibit the epithelial-mesenchymal transition of human liver cancer cell, and JNK-beta-catenin signaling pathway may be involved in EMT.

Key words: Liver cancer, Curcumin, ABT-737, Epithelial-mesenchymal transition

ZHENG Rui-nian, SUN Cheng-hui, JIA Yun, LIN Shun-huan, LIN Qin-xiong, LIU Chun, HAO Yan-yan, PAN Xue-bing, HE Yu, SHAO Jun-wei. The combined inhibiting effect and related mechanism of Curcumin and ABT-737 on epithelial-mesenchymal transition of human liver cancer cell[J]. Chinese Hepatolgy, 2022, 27(1): 86-90.

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