The Correlation Of MACC1,MRP And LRP With Cisplatin Resistance In Lung Adenocarcinoma

BackgroundLung adenocarcinoma is a malignant tumor that often occurs in bronchial mucosal epithelium or/and greater bronchial mucous glands of younger non-smoking women,without obvious clinical symptoms.Lung adenocarcinoma tissues grow slowly,but multiple metastases often occur in the early phase.Thus,chemotherapy is one of the main clinical treatments for lung adenocarcinoma.About one third of patients with it develop multidrug resistance after chemotherapy,which leads to chemotherapy failure.Multidrug resistance is a cross-drug resistance of tumor cells to various chemotherapy drugs.Multidrug resistance-associated protein（MRP）,lung resistance-related protein（LRP）,and metastasis-associated in colon cancer 1（MACC1）are associated with multidrug resistance of lung adenocarcinoma.Patients with lung adenocarcinoma show resistance to cisplatin,an essential drug to treat it,which directly leads to the poor efficacy of clinical chemotherapy.Therefore,there is an urgent need to develop new and more effective chemotherapeutic agents.ObjectiveTo investigate the resistance of lung adenocarcinoma cells to cisplatin,and to explore the correlation between MACC1,MRP and LRP and cisplatin resistance of lung adenocarcinoma,so as to provide laboratory reference for the clinical use of more effective cisplatin chemotherapy regimen for lung adenocarcinoma.Method1.Sampling and grouping:75 fresh specimens of lung adenocarcinoma resected were collected.None of the patients with it received preoperative radiotherapy and chemotherapy.Each specimen was divided into two parts.One part was cultured with primary cells in vitro,to detect the drug sensitivity test of lung adenocarcinoma cells to cisplatin by thiazoline-blue colorimetry（MTT）.In the other part,the expression of MACC1,MRP and LRP in adenocarcinoma tissues was detected by immunohisto-chemistry.2.Drug sensitivity test:MTT assay was used to detect the overall resistance of lung adenocarcinoma cells to cisplatin,and to investigate the resistance of lung adenocarcinoma cells to cisplatin at different differentiation degrees and TNM stages.3.Correlation between MACC1 expression and cisplatin resistance in lung adenocar-cinoma:Immunohistochemistry was used to investigate the expression of MACC1 protein in lung adenocarcinoma tissues,and to analyze the correlation between the expression and cisplatin resistance.4.Correlation between MRP expression and cisplatin resistance in lung adenocar-cinoma:Immunohistochemistry was used to investigate the expression of MRP protein in lung adenocarcinoma tissues,and to analyze the correlation between the expression and cisplatin resistance.5.Correlation between LRP expression and cisplatin resistance in lung adenocar-cinoma:Immunohistochemistry was used to investigate the expression of LRP protein in lung adenocarcinoma tissues,and to analyze the correlation between the expression and cisplatin resistance.6.Statistical methods:All experimental data were put into SPSS17.0 statistical software system for processing.T-test was used for comparison between groups;the correlation between differentiation degree,TNM stage and cisplatin resistance of lung adenocarcinoma was investigated by analysis of variance;the correlation between MACC1,MRP,LRP and cisplatin resistance of lung adenocarcinoma was investigated by Spaerman correlation analysis.Takeα=0.05 as examination standard.Result1.Among the 75 fresh specimens of lung adenocarcinoma resected,MTT test shows that 32 patients（42.67%）were resistant to 8.0μg.ml^-1cisplatin,33 patients（44.00%）were resistant to 6.0μg.ml^-1cisplatin,31 patients（41.33%）were resistant to 4.0μg.ml^-1cisplatin,23 patients（30.67%）were resistant to 2.0μg.ml^-1cisplatin.Resistance to 4.0μg.ml^-1cisplatin was more than that to 2.0μg.ml^-1cisplatin（P<0.05）,but there was no difference between resistance to 4.0μg.ml^-1cisplatin and resistance to 6.0μg.ml^-1cisplatin,and there was no difference between resistance to 6.0μg.ml^-1cisplatin and resistance to 8.0μg.ml^-1cisplatin.Cisplatin resistance was not correlated with differentiation degree and TNM stage to lung adenocarcinoma cells（P>0.05）.2.Immunohistochemical test showed that MACC1 expression results contained the following representation that 16 cases（21.33%）were“-”,21 cases（28%）were“+”,27cases（36.00%）were“++”,11 cases（14.67%）were“+++”in all lung adenocarcinoma tissues,and MACC1 expression was positively correlated with cisplatin resistance in lung adenocarcinoma cells（P<0.05）.3.Immunohistochemical test showed that MRP expression results contained the following representation that 11 cases（14.66%）were“-”,23 cases（30.67%）were“+”,32cases（42.67%）were“++”,9 cases（12.00%）were“+++”in all lung adenocarcinoma tissues,and MRP expression was positively correlated with cisplatin resistance in lung adenocarcinoma cells（P<0.05）.4.Immunohistochemical test showed that LRP expression results contained the following representation that 0 cases（0.00%）were“-”,25 cases（33.33%）were“+”,31cases（41.33%）were“++”,19 cases（25.34%）were“+++”in all lung adenocarcinoma tissues,and LRP expression was positively correlated with cisplatin resistance in lung adenocarcinoma cells（P<0.05）.Conclusion1.There is cisplatin resistance in lung adenocarcinoma.2.MACC1 expression was positively correlated with cisplatin resistance in lung adenocarcinoma cells,getting involved in mediating cisplatin resistance of lung adenocar-cinoma.3.MRP expression was positively correlated with cisplatin resistance in lung adenocarcinoma cells,getting involved in mediating cisplatin resistance of lung adenocar-cinoma.4.LRP expression was positively correlated with cisplatin resistance in lung adenocarcinoma cells,getting involved in mediating cisplatin resistance of lung adenocar-cinoma.