Tetrandrine Reverses Paclitaxel Resistance in Human Ovarian Cancer via Inducing Apoptosis, Cell Cycle Arrest Through β-Catenin Pathway

Abstract

Background

Paclitaxel (PTX) resistance is a great obstacle for the treatment of ovarian cancer. A previous study indicated that tetrandrine (TET) could induce the apoptosis of ovarian cancer cells. This study aimed to explore the effect of TET in combination with PTX on PTX resistance in ovarian cancer cells.

Materials and Methods

CCK-8 assay, flow cytometry and wound healing assays were used to detect the proliferation, apoptosis and migration of PTX-resistant SKOV3 cells (SKOV3/PTX). The expressions of Bax, Bcl-2, cleaved caspase 3, β-catenin, c-Myc, cyclin D1 and p21 in SKOV3/PTX cells were detected with Western blot. In vivo animal study was performed finally.

Results

In this study, the inhibitory effects of PTX on the proliferation and migration of SKOV3/PTX cells were markedly enhanced by TET. In addition, PTX-induced apoptosis in SKOV3/PTX cells was significantly enhanced by the treatment of TET via upregulating the levels of Bax and cleaved caspase 3, and downregulating the expression of Bcl-2. Moreover, combination of TET and PTX obviously induced cell cycle arrest in SKOV3/PTX cells via increasing the level of p21 and decreasing the levels of c-Myc and Cyclin D1. Meanwhile, combination of TET with PTX significantly decreased the expression of β-catenin in SKOV3/PTX cells. In vivo experiments further confirmed that TET enhanced the anti-tumor effect of PTX in SKOV3/PTX xenograft model.

Conclusion

We found that TET could enhance the sensitivity of SKOV3/PTX cells to PTX via inhibiting the β-catenin/c-Myc/Cyclin D1 signaling pathway. Therefore, PTX combined with TET might be considered as a potential approach for the treatment of PTX-resistant ovarian cancer.