SENSITIZATION OF HUMAN OSTEOSARCOMA CELL LINE 143B WITH CALCITRIOL FOR CISPLATIN THERAPY

Abstract

Background: Osteosarcoma (OS) is the most predominant bone tumor in individuals between 10-25 yrs of age. Cisplatin is the most widely used chemotherapeutic agent for OS management, it significantly enhances the survival rate. Resistance to the drug, toxicities of high doses and metastasis are the major concerns in the treatment. Objective: Our primary objective is to investigate effects of calcitriol in combination with cisplatin on the osteosarcoma cell apoptosis, invasion and migration. Our hypothesis is pretreatment of OS cells with calcitriol would sensitize them for cisplatin therapy leading to decrease in concentration for IC50. Secondary objective was to evaluate the effect of calcitriol on migration and invasion of OS cell lines, and the role of matrix metalloproteins (MMPs) in migration/invasion. Design: Previous findings in our lab suggests, calcitriol act as differentiation agent in human osteosarcoma cell lines 143B and SaOS-2. The dose response of cisplatin with and without calcitriol (100nM) pretreatment was studied in osteosarcoma cell lines 143B-MM, 143-P and control murine osteoblast MC3T3-E1. Cell proliferation and sensitization effects were evaluated by MTS assay. Boyden chamber assay was used for migration/invasion studies. MMP activity was measured using Sensolyte kit and real time PCR for the detecting the expression of MMP-1. Results: Calcitriol does not sensitize the 143B-P and 143B-MM OS cells for cisplatin therapy. Calcitriol sensitization inhibits the migration of 143B-P cells in matrigel whereas no significant difference was observed in control and calcitriol treated 143B-MM cells. Calcitriol pretreatment does modulate MMP-1expression in 143B-P OS cells. Conclusion: Calcitriol pretreatment does not sensitize OS cells to chemotherapy but, has an effect on the migration and invasion of 143B-P OS cell line.