Effect Of P110α Expression On Proliferation, Invasion And Migration Of Glioma Cell SHG44 And Its Molecular Mechanism

OBJECTIVE: p110α is an important member of PI3 K and is closely related to the occurrence and development of tumors.However,there is a little research on the relationship between p110α and glioma.This study aimed to investigate the expression of p110α in glioma cell and its effects on proliferation,invasion and migration of the glioma cell SHG44,and to explore its underlying molecular mechanism.METHODS: SHG44 cell proliferation was detected by cell counting kit(CCK8).Cell cratch test and Transwell invasion test were detected the effects of p110α on migration and invasion of SHG44 cell.The mRNA levels of p110α,AKT and mTOR in HEB cell group(normal glial cell)and SHG44 cell group(glioma cell)and PIK75(p110α-specific inhibitor)treatment SHG44 group were detected by real-time quantitative polymerase chain reaction(RT-qPCR).Western blot was used to detect the protein expressions of p110α,P-AKT,AKT,P-mTOR and mTOR in the HEB cell group and the SHG44 cell group and the PIK75 treatment SHG44 group.RESULTS: The results of CCK8 experiment showed that PIK75 with different concentrations could inhibit cell proliferation and presented dose-dependent manner(P<0.05).The results of scratch test showed that the migration rate of SHG44 cell in 0.25μmol/L PIK75 was 22.43%±1.55% significantly lower than that in the SHG44 cell group(54.12%±10.79%)(t =5.035,P<0.01).At the same time,the number of SHG44 penetrating cells inhibited by 0.25 μmol/L PIK75 in the Transwell invasion test was 20.67±1.22 significantly lower than that in the SHG44 cell group(44.33±1.90)(t=18.14,P<0.001).The protein expressions of p110α,P-AKT,AKT,P-mTOR and mTOR in SHG44 cell were all significantly higher than those in HEB cell(all P<0.05),and the mRNA levels of p110α,AKT and mTOR were all significantly higher than those of HEB cell(all P< 0.01).Compared with before treatment,the protein expressions of p110α,P-AKT,AKT,P-mTOR and mTOR decreased(all P<0.05)after SHG44 cell was treated with PIK75,which simultaneously companied with the mRNA levels of p110 a,AKT and mTOR were decreased(all P<0.01).CONCLUSION: The high expression of p110α in glioma can enhance the genetic transcription,protein translation and phosphorylation activities of AKT and mTOR,and then activates the PI3K/AKT/mTOR signaling pathway.Down-regulation of p110α expression can inhibit the proliferation,migration and invasion of SHG44 cell.p110α may be a new target for glioma drug therapy.