The Study Of Anti-human Glioma Cells By Temozolomide Combined With Targeted Drugs In Vitro

Background:The incidence rate of primary brain tumor is 2-19/100,000 people in the world. 60% for the gliomas,and the most of them are astrocytic tumor.Malignant brain tumor had became one of the tumors which resulting in death.Now the standard methods are post-operative radiotherapy,chemotherapy.Chemotherapy plays an important role in the whole progress and irreplaceable.However because of BBB, tumor heterogeneity and drug resistance,the effect of chemotherapy is poor.Conventional drug BCNU,DDP,VM-26s'effect is only 20%.Apply for the new drug Temozolomide,improve the chemotherapy effect,but the overall effect still disappointed. So solve the fundamental problem are develope new drugs continuously,optimize the chemotherapy methods and insist individual cure.Objective:Choose cultured human glioma cells as the object,trial drugs are Temozolomide and targeted drug-Cetuximab,perform the chemosensitivity study in vitro.Observe the effect of temozolomide and targeted drugs inhibite the human glioma cells, and the correlations between the chemosensitivity and patients characteristics were analyzed.In order to looking for effiective and new chemotherapy way,provide theoretical basis for guiding clinical medicine.Materials and Methods: At first,We collected 16 fresh astrocytic tumor specimens after operation and proved by pathology diagnosis from Department of Neurosurgery,First Affiliated Hospital Shanxi Medical University from Jan 2008 to Jun 2008. To produce monoplast suspension and carry out vitro primary culture,added solo durg with PPC in it,the combined drugs according to IC50.The sensitivity of cultured brain glioma cells to 2 chemotherapeutic drugs Temozolomide(TMZ) and Cetuximab(C225) combined or solo administration was determined by utilizing MTT colorimetric assay.Calculate the IR. The antineoplastic effects of these agents were compared, and the correlations between the chemosensitivity and patients characteristics were analyzed. By immunohistochemical technology, We detected the expression of MGMT protein in each patient's tumor tissue,under microscope 400 times count the positive cells to detect MGMT protein expression in each specimen.The correlation between the expression of the tumor and chemosensitivity with different drugs were analyzed.Providing evidence to individual cure in clinics.Results: The sensitivity of 16 cases were obtained. There was no significant difference in the chemosensitivity between of TMZ+C225 and C225+TMZ,but both of them were obviously higher than the two drugs only use. There was no significant influence of patients'pathological grade,age and sex of the tumor on chemosensitivity.In 16 cases ,75% of them were expressing MGMT.There was significant difference between Temozolomide and MGMT,other drugs with MGMT were no.Conclusion: It was significantly effective that temozolomide combined with targeted drugs against glioma cells,it is worth to explore deeply for applying to therapy human gliomas in clinics.In clinic,institute the chemotherapy way for the patients, there was no significant influence of patients'pathological grade,age and sex of the tumor on chemosensitivity.It can supply reference to test MGMT expression in the glioma by immunohistochemical technology for the patients who will accept the individual chemotherapy. Chemosensitivity test in vitro is valuable for select suitable drugs and institute individual cure way.It coule be increasing purposiveness of chemotherapy,avoiding the ineffective medicine,reducing the unnecessary burden on patients.