Explorative Study To Identify Novel Candidate Genes Related To Postchemotherapeutic Glioma Relapse Using Oligo Toxicology & Drug Resistance Microarray

Objective: To study the expression of toxicology & drug resistance gene and molecular related to stress response in pre-and post-chemotherapeutic glioma, and to explore novel candidate genes related to postchemotherapeutic glioma relapse.Methods: Ectopicly subcutaneous glioma transplantation models in nude mice were established by injection of human glioma cell line U251 cells. Tumor-beared nude mice were treated by the intraperitoneal injection of cisplatin (at the dose of 5mg/kg/d for 4-5 days continuously), chemotherapeutic and recurrent glioma model after chemotherapy were established. Gliomas were harvested as a group of gliomas after chemotherapy on the next day of completion of chemotherapy; about 1 week after chemotherapy gliomas were harvested as a group of smallest glioma after chemotherapy when gliomas significantly reduced but did not grow again ;about 10 to14 days after chemotherapy gliomas were harvested as a group of recurrence gliomas after chemotherapy when gliomas recurred rapidly. Expression of toxicology & drug resistance gene and molecular related to stress response in pre-and post-chemotherapeutic glioma were detected using oligo toxicology & drug resistance microarrays. Data in gene chip was analyzed by statistical software SPSS15.0.Results:Expression of ABCC1 increased gradually in gliomas after chemotherapy. Expression of ABCC5 and BCL2 increased in gliomas at completion of chemotherapy and significantly decreased when gliomas was smallest, and increased obviously when gliomas recurred. Expression of HSPB2 increased in gliomas after chemotherapy, its expression was highest when gliomas was smallest and decreased when gliomas recurred. Expression of NFKB1,NFKBIA and BAG1 decreased in gliomas at completion of chemotherapy and increased gradually subsequently. Expression of HSPA6 and PPARGC1A decreased in gliomas gradually after chemotherapy and increased again when gliomas recurred. NFKB1 and BAX were both positively correlated with PPARGC1A; BCL2 and HSPB2 were both negatively correlated with PPARGC1A and HSPB2 was negatively correlated with BAX too.Conclusion: 1. Expression of some genes related to toxicity and drug resistance in gliomas changed ambulatorily pre- and post-chemotherapy and there was a time window. ABCC1,ABCC5,HSPB2,NFKB1,PPARGC1A,ATM,BAG1 and BCL2 in gliomas are candidate genes which might play an important role in glioma recurrence after chemotherapy. 2. Activation of apoptosis gene of glioma cells after chemotherapy might correlate with PPARGC1A,NFKB and other stress-related genes,and expression change of these genes might relate to stress pathway.