Abstract

BackgroundChordoma was a typically slow-growing tumor. The therapeutic approach to chordoma had traditionally relied mainly on surgical therapy. And the main reason for therapeutic failure was resistance to chemotherapy and radiotherapy. However the refractory mechanism was not clear. The aim of this study was to investigate the expression of three genes (MDR1, HIF-1α and MRP1) associated with resistance to chemotherapy and radiotherapy in chordoma and chordoma cell line CM-319.Materials and methodsUsing immunohistochemical techniques, the expression of MDR1, HIF-1α and MRP1 was investigated in 50 chordoma specimen. Using RT-PCR and Western blot, the expression of MDR1, HIF-1α and MRP1 was investigated in chordoma and chordoma cell line CM-319.ResultsExpression of MDR1, HIF-1α and MRP1 was observed in 10%, 80% and 74% of all cases, respectively. Expression of MRP1 was correlated with HIF-1α. On the other hand, expression of MDR1 was not correlated with the expression of HIF-1α or MRP1. The expression of HIF-1α and MRP1 was observed, but MDR1 was not observed in chordoma and CM-319.ConclusionExpression of HIF-1α and MRP1 was observed in most chordoma specimen and CM-319 cell line; expression of HIF-1α correlated with MRP1. HIF-1α and MRP1 may play a role in the multidrug resistance of chordoma to chemotherapy.

Highlights

  • Chordoma, a primary malignant tumor of the skeleton, was considered to develop from a remnant of notochordal cells in the midline skeletal axis [1]

  • The expression of hypoxia-inducible factor alpha heterodimeric (HIF-1a) and multidrug resistanceassociated protein 1 (MRP1) was observed, but MDR1 was not observed in chordoma and CM-319

  • Expression of hypoxia-inducible factor (HIF)-1a and MRP1 was observed in most chordoma specimen and CM-319 cell line; expression of HIF-1a correlated with MRP1

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Summary

Introduction

A primary malignant tumor of the skeleton, was considered to develop from a remnant of notochordal cells in the midline skeletal axis [1]. The most common sites are the skull base and the sacrococcygeal region. It is typically slow-growing tumor, and initial symptoms are usually related to local progression of the disease with subsequent compression of adjacent structures. The therapeutic approach to chordoma has traditionally relied heavily on surgical control. Radiation therapy has been demonstrated to be a valuable modality for local control, with the advent of charged particle radiotherapy. The therapeutic approach to chordoma had traditionally relied mainly on surgical therapy. The main reason for therapeutic failure was resistance to chemotherapy and radiotherapy. The aim of this study was to investigate the expression of three genes (MDR1, HIF-1a and MRP1) associated with resistance to chemotherapy and radiotherapy in chordoma and chordoma cell line CM-319

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