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

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 βcatenin 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.

Identification of core genes for early diagnosis and the EMT modulation of ovarian serous cancer by bioinformatics perspective

“…Moreover, emerging evidence also suggests that dysregulation of cell cycle signaling cross-cascade is commonly been observed in a broad range of human cancers [ 34 , 35 ]. Especially, relevant co-DEGs were also most striking in cell cycle pathway associated highly with the tumorigenesis and progression of ovary cancer [ 36 , 37 ].…”

Tetrandrine Enhances H2O2-Induced Apoptotic Cell Death Through Caspase-dependent Pathway in Human Keratinocytes

“…Antioxidants are able to attenuate the damaging effects of ROS, and tetrandrine has been suggested to have potential as an antioxidant drug in (47). Studies have shown that tetrandrine induces cytotoxic effects through the induction of apoptosis of many types of human cancer cells in vitro (48,49). The relationship between tetrandrine-and H 2 O 2induced cell death remains underexplored.…”

The Wnt Signalling Pathway: A Tailored Target in Cancer

“…Ovarian Cancer (OC) is a global issue representing the fourth most common cancer in the female population, particularly in developed countries [ 115 ]. The poor survival rate is mainly due to the lack of screening methods at the early stages along with the absence of effective treatment options for advanced stages [ 116 ].…”

“…Jiang et al [ 115 ] have demonstrated that tetrandrine (TET) enhances the anti-tumour effect of paclitaxel (PTX) by decreasing c-myc and cyclin D1 and increasing p21 expression, resulting in cell cycle arrest. The pro-apoptotic effects of PTX+TET have also been investigated.…”

“…The pro-apoptotic effects of PTX+TET have also been investigated. TET was found to inhibit β-catenin downstream target genes by enhancing PTX activity and conferring sensitivity to PTX in resistant cells [ 115 ].…”