Human Menstrual Blood-Derived Stem Cells Inhibit the Proliferation of HeLa Cells via TGF-β1-Mediated JNK/P21 Signaling Pathways.

Qian-Yu Liu,Feng Ruan,Hou-Wen Chen,Jing-Yuan Li,Li Wei,Quan-Wen Liu,Ping Hu

doi:10.1155/2019/9280298

Abstract

Human menstrual blood-derived stem cells (hMBSCs) are a novel type of mesenchymal stem cells (MSCs) that have a high proliferative rate, multilineage differentiation potential, low immunogenicity, and low oncogenicity, making them suitable candidates for regenerative medicine. The therapeutic efficacy of hMBSCs has been demonstrated in some diseases; however, their effects on cervical cancer remain unclear. In the present study, we investigated whether hMBSCs have anticancer properties on cervical cancer cells in vivo and in vitro, which has not yet been reported. In vitro, transwell coculturing experiments revealed that hMBSCs suppress the proliferation and invasion of HeLa cervical cancer cells by inducing G0/G1 cell cycle arrest. In vivo, we established a xenografted BALB/c nude mouse model by subcutaneously coinjecting HeLa cells with hMBSCs for 21 days. We found that hMBSCs significantly decrease the average volume and average weight of xenografted tumors. ELISA, TGF-β1 antibody, and recombinant human TGF-β1 (rhTGF-β1) were used to analyze whether TGF-β1 contributed to cell cycle arrest. We found that hMBSC-secreted TGF-β1 and rhTGF-β1 induced cell cycle arrest and increased the expression of phospho-JNK and phospho-P21 in HeLa cells, which was mostly reversed by TGF-β1 antibody. These results indicate that hMBSCs have antitumor properties on cervical cancer in vitro and in vivo, mediated by the TGF-β1/JNK/p21 signaling pathway. In conclusion, this study suggests that hMBSC-based therapy is promising for the treatment of cervical cancer.

Highlights

Cervical cancer is a common malignancy and has been ranked as the second leading cause of cancer-related deaths in women [1], with about 52,900 new cases and 275,000 deaths every year [2, 3]
In the presence of bFGF (10 ng/ml), the Human menstrual blood-derived stem cells (hMBSCs) proliferate robustly and the average doubling time was 2 days (Figure 2(a)). hMBSCs were positive for mesenchymal stem cell markers CD29, CD73, CD105, and CD90 and negative for hematopoietic stem cell markers CD34 and CD45 as determined by flow cytometry (Figure 2(b)). hMBSCs expressed the major histocompatibility protein human leukocyte antigen (HLA)-ABC but none of its costimulatory molecules CD80, CD86, and CD40 nor major histocompatibility protein HLA-DR (Figures 2(b) and 2(c)), indicating that these cells possess low immunogenicity
Our results showed that hMBSCs express all of these pluripotent markers (Figure 2(d)), indicating hMBSCs have the capacity to selfrenew as well as multilineage differentiation potentials

Summary

Introduction

Cervical cancer is a common malignancy and has been ranked as the second leading cause of cancer-related deaths in women [1], with about 52,900 new cases and 275,000 deaths every year [2, 3]. Despite the improvement in preventative, diagnostic, and therapeutic strategies, the five-year survival rate for patients with advanced stages remains as low as 40%, resulting in a large number of cancer-related deaths [4, 5]. Stem cells are being explored as a promising candidate for cancer therapy. A series of studies have shown that MSCs play a critical role in regulating tumor initiation and progression by affecting the invasion, migration, or apoptosis resistance of tumor cells; the effects remain controversial.

Methods

Results

Conclusion