Effect Of All-trans Retinoic Acid On The Proliferation Of Glioma Cells

Glioma is the highest of intracranial tumor, and its pathogenesis is not clear. The maintreatments of glioma are still surgical operation, radiation therapy and chemotherapy, thebut failed to significantly improve survival time and quality of life of patients. The all-transretinoic acid (ATRA) can be effective in the treatment of acute promyelocytic leukemia(APL) treatment, in which ATRA by binding to retinoic acid receptors (RAR) to play itsrole, and the ATRA effects on solid tumors have also gradually been discovered. Theresearch on the effect of ATRA in the treatment of glioma is worth of further study.Objection: To study the influence of ATRA and RARα agonists or antagonists on theproliferation and migration of U251cells, and the expression of RARα. To explore thepossible RARα agonist and antagonist regulate the effect of the ATRA inhibited theproliferation of U251cells. In order to provide the basis for the ATRA as effective drug inthe treatment of glioma.Method:(1) U251cells were treated with ATRA at experimental concentrations of1μM,2.5μM,5μM,10μM,20μM for48h respectively. We detected the morphologicalchange and migration. MTT was used to examine cell proliferation.(2) The U251cellswere randomly divided into six groups including the control group, the ATRA of10μMgroup,the ATRA and BMS753of1μM group, the ATRA and Ro41-5253of1μM group,the ATRA and CD3254of1μM group, the ATRA and UVI3003of1μM group,Observation the cells morphological change in each groups; Then using MTT to test theinhibition effect of cells proliferation.(3) Western blot was used to analysis the expressionchanges of RARα and RXRαResult:(1) MTT and cell scratch showed that ATRA dose-dependently inhibited cellproliferation and migration compared with the control group. ATRA and BMS753enhanced inhibition of cell proliferation and migration of U251cells compared with theATRA group. ATRA and Ro41-5253reduced inhibition of cell proliferation and migrationof U251cells compared with the ATRA group.(2) The result of Western blot revealed that ATRA can increase the expression of RARα, but the expression of RXRα was nosignificant increase. ATRA and BMS753promoted elevated levels of RXRα expressioncompared with the ATRA group, ATRA and Ro41-5253decreased the expression of RARαcompared with the ATRA group. ATRA and CD3254increased the expression of RXRαcompared with the ATRA group. ATRA and UVI3003decreased the expression of RXRαcompared with the ATRA group.Conclusion: ATRA inhibited proliferation and migration of U251cells, the inhibitionis closely related to RARα receptors; RARα agonist BMS753can enhance the inhibitoryeffect of ATRA on U251cells, RARα antagonist Ro41-5253can weaken the inhibitoryeffect of ATRA on U251cells, which kinds of effects associated with expression levelsRARα receptor. The results provide an experimental basis for the feasibility of clinicalapplication of ATRA and combination therapy reducing the side effects for treatment ofglioma.