Research On Radiosensitity Of Lung Adenocarcinoma In Vitro To Inhibitor Of PI3K/Akt Injection

PrefaceLung cancer was divided mainly into two types: SCLC and NSCLC.80% of lung cancer is NSCLC which includes adenocarcinoma(25%), squamous-carcinoma(35%), undifferentiated carcinomar of megacell(15%)and others. Operation is a preferred therapeutic method,but 70-80% of patients who are diagnosed as lung carcinoma exactly, have been in advanced stage . .Radical operation has been impossible.So radiotherapy is one of the most important methods for unresectable carcinoma.Classical radiate cellular biology offered the theoretics foundation for developing new dose division,enhancing tumor cellular radisensitivity and protecting normal tissue. The molecule biology technique expansing,we have more comprehend to tumour radiomolecule biology for example repairs of DNA and signal transmit pathway. Using signal transmit pathway to advance tumor's radiosensitivity gain more and more attention.The article aimed at watching the radiosensitivity of the PI3K/AKT inhibitor.PurposeTo evaluate the radiosensitivity caused by LY294002 on culutured human lung adenocarcinoma cell line A549 and investigate the possible sensitization mechanism of LY294002. Materials and methodsThe experiment was divided into control(C)group, simple drug(D) goup, simple radiation(R)group and radiation plus drug (R+D)group. The cell cycles and cell apoptosis rates were analyzed by using FCM(Flow cytometry) in the different groups which were given single dose 6Gy radiation.The expression of pAkt and total Akt by western blot were detected.The cell survival curves were determined by cloning assay and cell clone technique for evaluating the cell lethal effects and by multitarget one—hit modelStatistical analysis was done with SPSS11.5 and Origin 6.0 software. The data was expressed as mean±SD,comparison among groups was performed by One-Way ANOVA,t-test and pearson linear correlation. Significance was accepted when p<0.05.ResultThe measure result of cell cycles by using FCM displayed that the percentage in G₂/M phase increased after A549 cell was given by LY294002 as well as single dose 6Gy radiation. The cell cycles in G₂/M phase were blocked significantly(p < 0.05),Apoptosis rates in the D group was higher than that in the R group, which was5.54times and3.9times than that in the C group. Apoptosis rates in the R+D group was the hightest and was6.67times than that in the C group(p<0.05).statistical analysis demonstrated that the percentage in G2/M phase had god relationship with apoptosis rates(rs=0.953, p<0.05).Ly294002 could partially inhibit phosphorylated AKT but not radiation.the combination of both could enhance the inhibition of phosphorylated AKT.Experiment result of radiosensitvity indicated that the ability of A549 cell forming colony in the testing group degraded contrasting with C group. With the increasing of radiation dose, forming colony ability decreased obviously. With the same radiation dose, colony rate in the R+D group was much less than that in the R group. The D₀ and D_q values were1.8973 and1.9188 in group, and in R+D group, the D₀ and D_q values were1.7005 andl.4349.The SER_D0 and SER_Dq were1.1157 , 1.3372,respectively.ConclusionLy294002 is a potential radiosensitizer for pulmonary adenocarcinoma cell line A549 in vitro.the main mechanism was that Ly294002 could partially inhibit pi3k/akt cellular transmit pathway and degraded akt's activity to alter the activity of albumen and enzymaty and adijust cellular period cellular angiogenesis in order to enhance radiosensitivity.