ShenLingLan Influences the Attachment and Migration of Ovarian Cancer Cells Potentially through the GSK3 Pathway.

Sioned Owen,Jian Chen,Yi Feng,Cong Wei,Yunong Gao,Huiming Zhang,Yiling Wu,Fiona Ruge,Jianqing Hou,Hongtao Wang,Yong Gao,Ying Yang,Wen Jiang

doi:10.3390/medicines4010010

Abstract

Background: Ovarian cancer presents a major clinical challenge in the UK. Glycogen synthase kinase-3 (GSK-3) has been linked to cancer. This study tested the impact of ShenLingLan (SLDM) on ovarian cancer cell behaviour and its links to GSK-3. Methods: Fresh ovarian tumours (n = 52) were collected and processed. Histopathologcial and clinical information were collected and analysed against GSK-3 transcript levels using quantitative PCR (qPCR). Immortalised ovarian cancer cells’ protein alterations in response to SLDM were identified using a Kinexus™ protein kinase array. The effects of SLDM and a combination of SLDM and TWS119 on ovarian cancer cells ability to attach and migrate were evaluated using electrical cell-substrate impedance sensing (ECIS). Results: Transcript expression of GSK-3β was significantly increased in ovarian tumours which were poorly differentiated, patients with recurrence and in patients who had died from ovarian cancer. Treating SKOV-3 ovarian cells with SLDM reduced GSK-3 expression and GSK-3α (Y279). Treatment with SLDM reduced ovarian cancer cells ability to attach and migrate, which was further reduced in the presence of TWS119. Conclusions: This study identified a potential mechanism by which SLDM may exert anti-metastatic effects. Further work is needed to investigate the in vivo effects SLDM has on ovarian tumours.

Highlights

Ovarian cancer incidence in women within the UK has increased by 17% since the 1970s and it is the fifth most common cancer-related death, though it is the seventh most common cancer type diagnosed [1]
Expression of GSK3β was linked to a poor clinical outcome. In this relatively small clinical cohort, we found that levels of GSK3β transcripts were significantly higher in patients with ovarian cancer–associated recurrence (p < 0.05 vs. incidence free) and in patients who died of ovarian cancer (p < 0.05 vs. patients who are alive) (Figure 5B,C, respectively)
GSK‐3 plays in a variety of are diseases aredue extensive due to of thephosphorylation vast array of Glycogen synthase kinase-3 (GSK-3) plays in a variety of diseases extensive to the vast array phosphorylation and pathways it can regulate

Summary

Introduction

Ovarian cancer incidence in women within the UK has increased by 17% since the 1970s and it is the fifth most common cancer-related death, though it is the seventh most common cancer type diagnosed [1]. Glycogen synthase kinase-3 (GSK-3) has two highly conserved members, GSK3A and GSK3B, which result in a 51 kDa and 47 kDa protein, respectively [5]. Both have been identified as critical enzymes involved in a variety of cellular processes, some of which are disrupted in cancer, including cell cycle progression, differentiation, migration and survival [6]. Glycogen synthase kinase-3 (GSK-3) has been linked to cancer. This study tested the impact of ShenLingLan (SLDM) on ovarian cancer cell behaviour and its links to GSK-3. Results: Transcript expression of GSK-3β was significantly increased in ovarian tumours which were poorly differentiated, patients with recurrence and in patients who had died from ovarian cancer.

Methods

Results

Conclusion