Mesenchymal stem cells derived from normal gingival tissue inhibit the proliferation of oral cancer cells in vitro and in vivo

Ji,Xiaoli; Zhang,Zhihui; Han,Ying; Song,Jiangyuan; Xu,Xiangliang; Jin,Jianqiu; Su,Sha; Mu,Dongdong; Liu,Xiaodan; Xu,Si; Cui,Hongwei; Zhao,Zhongfang; Wang,Yixiang; Liu,Hongwei

doi:10.3892/ijo.2016.3715

Mesenchymal stem cells derived from normal gingival tissue inhibit the proliferation of oral cancer cells in vitro and in vivo

Authors:
- Xiaoli Ji
- Zhihui Zhang
- Ying Han
- Jiangyuan Song
- Xiangliang Xu
- Jianqiu Jin
- Sha Su
- Dongdong Mu
- Xiaodan Liu
- Si Xu
- Hongwei Cui
- Zhongfang Zhao
- Yixiang Wang
- Hongwei Liu
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Affiliations: Department of Oral Medicine, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China, Department of Stomatology, Peking University Third Hospital, Haidian, Beijing 100191, P.R. China, Department of Stomatology, Wuhan Union Hospital, Wuhan, Hubei 430022, P.R. China, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China, Central Laboratory, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China
Published online on: September 28, 2016 https://doi.org/10.3892/ijo.2016.3715
Pages: 2011-2022

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Abstract

The interplay between tumor cells and mesenchymal stem cells (MSCs) within tumor microenvironment plays a significant role in tumor development, and thus might be exploited for therapeutic intervention. In this study, we isolated MSCs from normal gingival tissue (GMSCs), and detected the effect of GMSCs on oral cancer cells via direct co-culture and indirect co-culture systems. The cell proliferation assay of direct co-culture showed that GMSCs could inhibit the growth of oral cancer cells. Conditioned medium derived from GMSCs (GMSCs-CM) also exerted an anticancer effect, which indicates that soluble factors in GMSCs-CM played a dominant role in GMSCs-induced cancer cell growth inhibition. To investigate the mechanism, we performed apoptosis assay by flow cytometry, and confirmed that cancer cell apoptosis induced by GMSCs could be a reason for the effect of GMSCs on the growth of oral cancer cells. Western blotting also confirmed that GMSCs could upregulate expression of pro-apoptotic genes including p-JNK, cleaved PARP, cleaved caspase-3, Bax expression and downregulate proliferation- and anti-apoptosis-related gene expression such as p-ERK1/2, Bcl-2, CDK4, cyclin D1, PCNA and survivin. Importantly, the inhibitory effect of GMSCs on cancer cells can partially be restored by blockade of JNK pathway. Moreover, animal studies showed that GMSCs exerted an anticancer effect after oral cancer cells and GMSCs were co-injected with oral cancer cells. Taken together, our data suggest that GMSCs can suppress oral cancer cell growth in vitro and in vivo via altering the surrounding microenvironment of oral cancer cells, which indicates that GMSCs have a potential use in the management of oral dysplasia and oral cancer in future.

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