The Role Of LRIG1in Chemosensitivity And Its Possible Mechanism In Human Glioma

Background and objective:Glioma is the most common primary central nervous system maligant tumor, it is difficult to treat and it is a serious threat to the patients. Along with the emergence of temozolomide(TMZ), the effect is better than before. Many studies have confirmed that TMZ can enhance the median survival of glioma patients. But the drug resistance of glioma restrict the clinical curative effect of TMZ,especially the multidrug resistance(MDR). LRIG1is a RTK inhibitor which is found in recent years.LRIG1is expressed in various human tissues and it is highly expressed in human brain. In recent years, many studies have confirmed that LRIG1can inhibit the proliferation of human glioma cells and it is a new tumor suppressor gene. But the relationship between LRIG1and glioma chemosensitivity is still unknown. The purpose of this study is to explore the relationship between LRIG1and glioma chemo sensitivity.Methods:Specimens from98astrocytic tumors in93patients were collected at the Renmin Hospital of Wuhan University from April2009to January2011. We detected the expression of LRIG1and BCL-2(part I); We established a multidrug resistance cell line(U251/MDR) and detected the expression of LRIG1and BCL-2(part II); We detected the multidrug resistance after LRIG1was up-regulated or down-regulated(part Ⅲ); We depleted U251/MDR cells of LRIG1using siRNA after we had depleted the cells of BCL-2by siRNA(part Ⅳ).Results:The expression of LRIG1was up-regulated and BCL-2expression was down-regulated in human glioma tissues. The multidrug resistant cell line U251/MDR was isolated by stepwise exposure to increasing VP-16concentrations. The expression of LRIG1was up-regulated and BCL-2expression was down-regulated in U251/MDR cells. The chemosensitivity was enhanced after LRIG1plasmid was transfected into U251/MDR cells. After LRIG1was knocked down, the chemosensitivity was decreased; We depleted U251/MDR cells of LRIG1using siRNA after we had depleted the cells of BCL-2by siRNA. Results showed that the effect of siBCL-2was lost when LRIG1expression was also reduced.Conclusions:LRIG1can enhanced the chemosensitivity by modulating BCL-2expression in glioma cells.