Inhibition of α folate receptor resulting in a reversal of taxol resistance in nasopharyngeal carcinoma

Otolaryngol Head Neck Surg. 2012 Feb;146(2):250-8. doi: 10.1177/0194599811426260. Epub 2011 Oct 31.

Abstract

Objective: To further determine the role of FOLR1 in taxol resistance of nasopharyngeal carcinoma (NPC) and whether inhibition of FOLR1 expression reverses the taxol-resistant phenotype.

Study design: Correlation study between gene expression and cancer cell survival.

Setting: University hospital.

Subjects and methods: Three taxol-resistant sub-cell lines with a different resistant index were established from the parental CNE-1 NPC cell line. The correlation between FOLR1 expression and taxol sensitivity was statistically analyzed. Inhibition of FOLR1 expression was carried out by RNA interference and by a FOLR1-specific monoclonal antibody, and taxol sensitivity was examined by colony formation assays. FOLR1 expression was also examined in 72 NPC patient specimens by immunohistochemistry.

Results: The levels of FOLR1 expression were positively and significantly correlated with a taxol resistance phenotype (P < .05). Inhibition of FOLR1 expression resulted in a significantly increased sensitivity of taxol to taxol-resistant NPC cells (P < .05). An increase of FOLR1 expression by gene transfection caused a taxol-resistant phenotype in parental NPC cells. The level of FOLR1 expression was found to be related to clinical stage in NPC tissue samples.

Conclusion: These results suggest that FOLR1 plays an important role in taxol resistance of NPC cells.

Keywords: folate receptor; nasopharyngeal carcinoma; taxol resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Carcinoma
  • Drug Resistance, Neoplasm / drug effects
  • Folate Receptor 1 / antagonists & inhibitors*
  • Folic Acid
  • Humans
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / drug therapy*
  • Nasopharyngeal Neoplasms / metabolism
  • Paclitaxel / therapeutic use*
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Phytogenic
  • FOLR1 protein, human
  • Folate Receptor 1
  • Folic Acid
  • Paclitaxel