The effect of Sclareol on the expression of MDR-1 gene and Glycoprotein-P Level in MKN-45 human gastric cancer cells

Abstract

Background & Aims: In recent years, the emergence of multidrug resistance in gastric cancer has been a major challenge in treatment of gastric cancer. To deal with the problem, studies and researches were conducted on Sclareol and have turned up the anti-cancer effect of the compound and have also determined the molecular mechanism of it to some extent. Therefore, the main purpose of this study was to investigate the effect of the substance extracted from Salvia Officinalis called Sclareol on MDR-1 gene expression and consequently on the rate of P-glycoprotein in human gastric cancer cell line MKN-45. Materials and Methods: Cell line MKN-45 was purchased from the Pasteur Institute of Iran and cultured in complete RPMI 1640 Medium with Fetal Bovine Serum, with 20, 40, 60, 80 and 100 μM concentrations of Sclareol treatment for 5 hours. The rate of expression of MDR-1 gene was assessed by Real Time-PCR method and that of P-GP was assessed by Western blotting method. Results: The expression of MDR-1 gene was significantly reduced at doses of 20, 40 and 60 μmol of Sclareol, while at doses of 80 and 100 μmol there was not seen much effect (p <0.0001). Also, P-glycoprotein showed a very high decrease at doses of 40 and 60 μmol of Sclareol, but no decrease was seen at doses of 80 and 100 μmol (p <0.0001). Conclusion: From the results of this study, it seems that doses between 20 and 60 μmol of Sclareol can be useful in reducing drug resistance, but doses above 60 mmol do not have such an effect.

Keywords

• gastric cancer
• sclareol
• multi-drug resistance (mdr1) gene
• glycoprotein-p