The effect of endogenous bone marrow derived mesenchymal stem cells on the activity of β-catenin signaling pathway on chemotherapy resistance of osteosarcoma

Abstract

This study assesses the effect of bone marrow derived mesenchymal stem cells (BMSC) on chemotherapy resistance of osteosarcoma. 60 SPF mice were randomly separated into control group and model group. Serum alkaline phosphatase (ALP), Calcium (Ca), Phosphorus (P) and tumor formation rate were observed. The osteosarcoma tissues were taken to construct drug-resistant osteosarcoma cell lines. Control group, 5-fluorouracil (5-Fu) group, BMSC group, 5-Fu+BMSC group, and then set 5-Fu+BMSC+agonist group, 5-Fu+BMSC+inhibitor group, respectively. Osteosarcoma cell sensitivity to 5-Fu (IC50) and β-catenin/p-β-catenin expression were examined. Compared with control group, the ALP level and tumor formation rate in model group were higher and P level was remarkably lower. Ca level showed no difference between two groups (P >0.05). The 5-Fu+BMSC group and 5-Fu group had the highest IC50 levels and the control group and BMSC group had the lowest IC50 levels. The β-catenin/p-β-catenin expressions were the highest in 5-Fu+BMSC group and 5-Fu group, and their expressions in control group and BMSC group were the lowest. 5-Fu+BMSC+agonist group showed higher β-catenin, p-β-catenin and IC50 levels, which are lower in 5-Fu+BMSC+inhibitor group. Endogenous BMSC can promote the chemotherapy resistance of osteosarcoma. They can promote β-catenin and β-catenin phosphorylation level, down-regulate osteosarcoma cell sensitivity to 5-Fu, and then promote drug resistance. Therefore, β-catenin signaling can be used as a target to reverse the resistance of osteosarcoma cells to 5-Fu.