1. ¹Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China
2. ²Department of Cancer Research, Institute for Molecular Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China
3. ³Department of Cell Biology, Centre of Excellence in Tissue Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100073, China

Correspondence: Xiaodong Zhang, Tel: +86-22-23506830; Fax: +86-22-23501385 E-mail: zhangxd@nankai.edu.cn; Lihong Ye, Tel: +86-22-23501385; Fax: +86-22-23501385 E-mail: yelihong@nankai.edu.cn; Robert C Zhao, Tel: +86-10-65125311; Fax: +86-10-65125311 E-mail: chunhuaz@public.tpt.tj.cn

Received 16 February 2007; Revised 15 June 2007; Accepted 7 November 2007.

Abstract

Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines (H7402 and HepG2) using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen (PCNA) and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that -catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.