Studies on the effect of Celastrus orbiculatus (Celastraceae) extract on chemosensitivity of liver cancer cells via Wnt/β-catenin pathway

Abstract

Purpose: To examine the efficacy of Celastrus orbiculatus extract (COE) on the chemosensitivity of liver cancer (LC) cells and its mechanism of action.Methods: Hep G2/ADM cells in the logarithmic growth phase were assigned to a control group (no treatment for cell culture medium only) and a study group (120 μg/ml COE added to the culture medium). After 48 h of incubation, the biological responses were compared. The study group wasdivided into groups A and B, while control group was divided into groups C and D, with 1 μmol/L XAV939 added in groups A and C. Cell proliferation, cell invasion, cell apoptosis rate, and apoptosis protein in the four groups were evaluated.Results: The study group showed significantly lower values in terms of cell proliferation and cell invasiveness (p < 0.05) and a higher apoptotic rate than the control group (p < 0.05)). The study group also demonstrated an elevated pro-apoptotic protein Bax level and a declined anti-apoptotic protein Bcl-2  level. In contrast to group B, the proliferation and invasiveness of Hep G2/ADM cells in group A treated with the inhibitor, XAV939, were significantly lower (p < 0.05), while the apoptotic rate exhibited a significant increase (p < 0.05). There was a rise in the level of pro-apoptotic protein, Bax, and a fall in the anti-apoptotic protein Bcl-2 level in group A. Lower levels of β-catenin, c-Myc, and cyclin D1 protein were observed in the study group compared with the control group (p < 0.05). Compared with other groups, the multiplication capacity and invasiveness of cells in group A treated with COE and inhibitor XAV939 significantly declined, while the apoptotic rate increased (p < 0.05).Conclusion: COE reverses drug resistance in chemotherapy by inhibiting the expression of Wnt/β-catenin pathway in LC cells. Therefore, COE has potentials for use along with chemotherapeutic agents in the management of liver cancer.