Expression And Correlation Analysis Of Multidrug Resistance Protein And Mismatch Repair Gene In Esophageal Squamous Cancer

Esophageal squamous cancer is one of the most common cancers,chemotherapy after operation is one of effective treatment.Then multidrug resistance(MDR) of cancer cells is a major cause of failure in chemotherapy.However,till now the mechanism remains unclear. We discovery multidrug resistance of tumor cells is a complex developmental process that involves proto- or anti-oncogene,Cell cycle and regulation factor,apoptosis relevant factors,ect.It has been found that mismatch repair gene is related to multiple drug resistance in recent years.Most investigation hint that it is related to multiple drug resistance and Multidrug Resistance Protein.The usual of them are p-glycoprotein, glutathione S-transferaseπ,DNA topoisomeraseⅡ.They take part in drug resistance by decreasing the concentration or toxicity of drug in cellsand changing the target of drug.The mismatch repair system plays key role in maintain fieldity of DNA replication and control genovariation by repaire mismatch of DNA Bases.When function defects of mismatch repair genes,Cell Showes Genomic instability because of the aggregation of mutation. People begin to pay close attention to the role of multidrug related protein in drug resistant cell line.and have found that function defects of mismatch repair genes have relation to antagonism effects of alkylating agents and platinum drugs in malignant cells.It is rarely to be reported for the research of co - expression and clinical significance of multidrug related protein and mismatch repair gene in esophageal carcinoma.In order to further investigate their relationship,we detected the expression of P-gp,GST-π,TopoⅡand the expression of hMLH1 and hMSH2 respectively in esophageal carcinoma from 144 patients and 30 normal mucosa tissues by SP immunohistochemistry.The following is the results and conclusions.1.The expression of P-gp,GST-πand TopoⅡin esophageal squamous cancer were significantly higher than that in normal mucosa tissue,which was related to the differentiated degree of carcinoma.P-gp,GST-πwere more expressed in well-differentiated cancer and TopoⅡwere more expressed in poorly differentiated cancer.The three protein were all related to the drug resistance to esophageal squamous cancer,which were more powerful with the more better differentiation.2.The rate of coexpression of P-gp,GST-πwas 50.7%(73/144),The rate of coexpression of TopoⅡand P-gp,GST-πwere 11.8%(17/144),7.6%(11/144).It hints that there is regulatory mechanism and correlative dependence between P-gp and GST-π.The TopoⅡdrug resistance may be different from P-gp and GST-π.So,the expression of P-gp,GST-πand TopoⅡshould be detected before chemotherapy,which may be benefit the selection of sensitive drugs to to aim directly at esophageal squamous cancer.3.The expression of hMLH1 and hMSH2 in esophageal squamous cancer were significantly less than that in normal mucosa tissue,which was related to the histological grade.It hints that the expressive depletion of hMLH1 and hMSH2 resulted from gene mutation may be related to esophageal squamous carcinogenesis,this may be an early event.The expression absence of mismatch repair was related to the differentiated degree of esophageal squamous cancer.DNA microsatellite instability dued to mismatch repair gene mutation may be another molecular mechanism of esophageal squamous carcinogenesis.4.The P-gp and GST-πprotein were more expressed when the hMLH1 and hMSH2 were absent,which caused accentuation of drug pump effect and attenuation of drug toxicity.Thereby,the drug resistance of chemotherapeutics was increasing.At the same time,the decreased targets of chemotherapeutics dued to the low TopoⅡexpression also induces drug resistance.It hints that mismatch repair defect resulted from hMLH and hMSH2 gene mutation may lead to the drug resistance to esophageal squamous cancer through an different expression effect of P-gp,GST-πand TopoⅡ.