白藜芦醇对MKN-45人胃癌细胞耐多药-1基因表达及糖蛋白p水平的影响

S. Bordbar-Bonab, Soltanali Mahbob, Morteza Vahed-Jabari, H. Dolatkhah
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摘要

背景与目的:近年来,胃癌多药耐药的出现是胃癌治疗面临的重大挑战。针对这一问题,人们对其进行了研究,发现了该化合物的抗癌作用,并在一定程度上确定了其分子机制。因此,本研究的主要目的是研究鼠尾草提取物Sclareol对人胃癌细胞株MKN-45中MDR-1基因表达及p -糖蛋白表达率的影响。材料和方法:MKN-45细胞系购自伊朗巴斯德研究所,在含胎牛血清的RPMI 1640培养液中,分别用浓度为20、40、60、80和100 μM的Sclareol处理5小时。采用Real - Time-PCR法检测耐多药-1基因表达率,Western blotting法检测P-GP基因表达率。结果:20、40、60 μmol剂量下,MDR-1基因表达明显降低,80、100 μmol剂量下影响不明显(p <0.0001)。p -糖蛋白在40和60 μmol剂量下均有显著降低,而在80和100 μmol剂量下无显著降低(p <0.0001)。结论:从本研究结果来看,剂量在20 ~ 60 μmol之间的Sclareol可有效降低耐药,而剂量在60 μmol以上的则无此作用。
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The effect of Sclareol on the expression of MDR-1 gene and Glycoprotein-P Level in MKN-45 human gastric cancer cells
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.
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