Bone Marrow Mesenchymal Stem Cells Inhibit Prostate Cancer Cell Proliferation and Promote Apoptosis

Abstract

Bone marrow mesenchymal stem cells (BMSCs) have the potential to multipolarize and closely related to cancer cell proliferation and apoptosis. This study investigated the mechanism by how BMSCs interacts with ERK1/2 signaling pathway to regulate PC cell growth. PC cells were implanted into rats to establish animal model of PC and then administered with normal saline, BMSCs, BMSCoverexpressed miR-21, and miR-21 inhibitor U0126 (control group, BMSCs group, BMSCs+ERK1/2 group, and U0126+BMSCs+ERK1/2 group) followed by analysis of weight and tumor volume, colony formation assay, proliferation and apoptosis as well as the expression of ERK1/2 signaling proteins and miR-21. Treatment with BMSCs and BMSCs+ERK1/2 significantly suppressed tumor growth. The tumor volume of rats in the U0126+BMSCs+ERK1/2 group was lowest among all groups (p < 0.05). Compared with control group, BMSCs group had the less number of clone formation, but more than U0126+BMSCs+ERK1/2 group (p < 0.05). U0126+BMSCs+ERK1/2 group had the least number of clone formation. As BMSCs treatment promoted PC cell apoptosis and suppressed cell cycle, overexpression of miR-21 reduced apoptosis and accelerated cell cycle which was abolished by addition of U0126. U0126+BMSCs+ERK1/2 group and BMSCs+ERK1/2 group had lowest and highest expression of miR-21, respectively. Highest tERK1 and tERK2 levels were found in control group and highest p-ERK1 and p-ERK2 levels in BMSCs+ERK1/2 groups. The protein levels of tERK1, tERK2, p-ERK1 and p-ERK2 upon treatment with BMSCs were higher that of U0126+BMSCs+ERK1/2 group (p < 0.05). In conclusion, BMSCs decelerate cell cycle, inhibit cell proliferation and promote apoptosis of PC cells via regulation of ERK1/2 signaling and reverse the impact of miR-21 on PC cells.