The Study Of Gefitinib Combined With Temozolomide Inhibits In Vitro Human Giloma Cell Proliferation

Background:The annual incidence of primary brain tumors was 10/10 million people, intracranial tumors occupy aboutl.8% of the tumor in the body, accounted for 2.35% of death caused by malignant tumors, in the tenth place.While about 60% of primary intracranial tumors are glial cell tumors. The main treatment of glioma is surgery, combin-d with comprehensive treatment of radiotherapy and chemotherapy. But even with microsurgical surgery could not fully remove the tumor, so glioma often recurrent, the treatments of glioma are not satisfactory. The median survival of high-level malignant glioma after diagnosis was 9 to 12 months, and these patients were under surgical resection, radiotherapy, chemotherapy and other active treatments. Postoperative chemotherapy is an important therapeutic tool in the treatments of gliomas which is irreplaceable. Traditional chemotherapy is mainly in all kinds of cytotoxic agents.Drugs of high-fat-soluble, small molecular weight, non-ionizing, short duration of action, can across the blood-brain barrier and to normal brain tissue little toxicity can be used in the treatment of intracranial tumors. The majority view is that combined chemotherapy is better than monotherapy. Temozolomide is a second generation of alkylating agent, it can easily through the blood-brain barrier and well tolerated, and toxicity with other drugs are not superimposed, it improve the current situation of the low rate of glioma chemotherapy in some part,now it is the first choice in chemotherapy for malignant glioma.Targeted therapy of gliomas, a new direction in recent years, are the new direction in the treatment of glioma. Gefitinib is an EGFR (epidermal growth factor receptor) tyrosine kinase inhibitors, which inhibit the tumor cells through the EGFR signaling pathway initiated by anti-tumor effect of play. The side effects of targeted therapy is little, so Gefitinib may be the ideal drug in the treatment of glioma, such as whether it can enhance the sensitivity of conventional chemotherapy drugs, whether combined chemotherapy is better than monotherapy are remained to be further confirmed.Purpose:The human glioma cell line U251 (WHO IV grade) and SHG-44 (WHOⅡgrade) are sub cultured. We detect the EGFR gene expression in glioma cell lines. Select Temozolomide (Temozolomide, TMZ) which is the current first choice drug for the chemotherapy of glioma, and gefitinib (Gefitinib, ZD1839) which is molecular targeted drug of EGFR receptor inhibitor. We make drug sensitivity tests in vitro, and make an observation of temozolomide and gefitinib on human Inhibition of glioma cells according to the EGFR expression and to evaluate the combined effect of the two drugs. We estimates the efficacy in combination of temozolomide and EGFR targeted drugs in different grade gliomas preliminarily to explore a new type of individual chemotherapy,which will provide a theoretical basis for glioma in order to guide the clinical application of combined chemotherapy.Materials and Methods:Two different malignant glioma cell lines U251 (WHO IV grade) and SHG-44 (WHOⅡgrade) were cultured In vitro, detect the EGFR gene expression in cells through literature review. Use the application of MTT to assay cells to cancer chemotherapeutic agent TMZ, ZD1839, TMZ+ZD1839 Drug sensitivity, calculate the inhibition rate (IR), use the application of flow cytometry to detect the cell cycle and the change of apoptosis rate.Make comparison of the effect with monotherapy alone and combined chemotherapy in vitro. Sorting data analysis, processing data with statistical software.Results:Results showed that glioma cell lines with different EGFR expression is different, U251 cell lines expressing high, SHG-44 cell lines expressing low. The inhibition of TMZ combined with ZD1839 in U251 glioma cell lines was significantly better than single drug use (P<0.05), inhibition of tumor cells was significantly higher than single drug use, apoptosis in drug treatment was significantly increased, with the increase of drug concentration.Conclusions:Temozolomide combined molecular targeting drug gefitinib inhibit glioma cells more than single drug application, for the high rate of EGFR expression in glioma tumors, the combin-d therapy was significantly inhibited. The chemical treatment of gliomas deserves further study to apply it to clinical treatment of human brain. In vitro susceptibility testing in clinical chemotherapy can increase the purpose of guiding the chemical treatment of the different grade gliomas, the development of individual chemotherapy are of great value.