The Impact of Melatonin on Colon Cancer Cells' Resistance to Doxorubicin in an in Vitro Study

Int J Mol Sci. 2017 Jun 29;18(7):1396. doi: 10.3390/ijms18071396.

Abstract

Multi-drug resistance (MDR) is the main cause of low effectiveness of cancer chemotherapy. P-glycoprotein (P-gp) is one of the main factors determining MDR. Some studies indicate the potential role of melatonin (MLT) in MDR. In this study, we examined the effect of MLT on colon cancer cell's resistance to doxorubicin (DOX). Using the sulforhodamine B (SRB), method the effect of tested substances on the survival of LoVo (colon cancer cells sensitive to DOX) and LoVoDX (colon cancer cells resistant to DOX) was rated. Using immunocytochemistry (ICC), the expression of P-gp in the LoVo and LoVoDX was determined. With the real-time PCR (RT-PCR) technique, the ABCB1 expression in LoVoDX was evaluated. Based on the results, it was found that MLT in some concentrations intensified the cytotoxicity effect of DOX in the LoVoDX cells. In the ICC studies, it was demonstrated that certain concentrations of MLT and DOX cause an increase in the percentage of cells expressing P-gp, which correlates positively with ABCB1 expression (RT-PCR). The mechanism of overcoming resistance by MLT is probably not only associated with the expression of P-gp. It seems appropriate to carry out further research on the use of MLT as the substance supporting cancer chemotherapy.

Keywords: P-glycoprotein; doxorubicin; melatonin; multi drug resistance.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / drug effects*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / physiopathology*
  • Doxorubicin / therapeutic use
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melatonin / metabolism
  • Melatonin / therapeutic use*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Doxorubicin
  • Melatonin