The Inhibition Of Celecoxib On Human Gliomas And Its Molecular Mechanism

Part oneExpression of COX-2 and Its Relationship with Apoptosis and Prolifteration, P-GP in Human GliomasObject To investigate the expression of cyclooxygenase-2 (COX-2) in astrocytomas, and analyze the correlation between that and apoptosis, prolifteration of the astrocytomas. MethodsThe expression of COX-2 and proliferating cell nuclear antigen (PCNA), P-GP was detected by immunohistochmical (S-P) method in 80 astrocytomas and 10 cases normal brain tissue. Apoptosis cells were detected by TUNEL.Results The positive expression rate of COX-2 in astrocytomas wassignificantly higher than that in the control group, which was related to pathological feature of astrocytomas. PI in astrocytomas was significantly higher than that in the control group and PI in COX-2 positive group was significantly higher than that in negative group. AI in astrocytomas was significantly higher than that in the control group and AI in COX-2 positive group was significantly lower than that in negative group. P-GP in astrocytomas was significantly higher than thatin control group (P<0. 05) .Expression rates of P-GP in COX-2 positive and negative groups were 73.91% and 50.00% resepetively. ConclusionOverexpression of COX-2 in the astrocytomas can inhibit cell apoptosis, and induce astrocytomas proliferate, and COX-2 is related to chemotherapy of gliomas, so play an important role in tumor development and progression.Part two Effect of Celecoxib on the Chemo-sensitivity in U251 Cell lines of GliomasObjective To investigate the effect of Celecoxib on the Chemo-sensitivity in U251 cell lines of gliomas, and the inhibition on human gliomas. Methods U251 cells were divided into 4 groups: A,Celecoxib cells; B, ADM cells; C, ADM+Celecoxib cells; D, control cells. The inhibition rates were dectected by MTT. The expression of P-GP and MDRi mRNA was detected by Western-blot and reverse transcription-polymerase chain reaction (RT-PCR) respectively. Results Combined useof Celecoxib and ADM could inactivate synergistically U251 cells. The expression of the P-GP and MDRI in the B group is higher than the otherthree groups. Conclusion Celecoxib can present a synergistic with ADM, so it has a promising prospect in clinical use of gliomas.Part threeThe Effect of Celecoxib on Angiogenesis and Cell Cycle onGliomasObjective To investigate the effect of Celecoxib on the angiogenesis in U251 Cell line of Gliomas. Methods U251 mouse were divided into 2 groups, control group and Celecoxib group. 4 weeks laters, the weights of the tumor wre measured respectively. The apoptosis of the tumors were detected by flow cytometry (FCM). microvessel density was examined(MVD) by immunohistochmical (S-P) method. Results The tumors were typic glioblastomas on pathology. The MVD of Celecoxib and control group was (25. 7 ± 3.25)/HP and (76. 4 ± 9. 41)/HP respectively. Weights of 2 groups of tumor were 151.3 ± 23.85) mg and (325.2 ±37.34) mg respctively, and apoptosis cell in Celecoxib group was more than that in contral group. The cells at S and G₂ phase in Celecoxib group were more than that in control group, and cells at G₁ phase in Celecoxib group were less than that in control group. Conclusion Celecoxib can inhibit angiopiesis of U251 gliomas ceil lines in vivo, and induce the cell apoptosis and arres(?) cell at G₁ phase, so it has a promising prospect in clinical use of gliomas.