Analysis Of Different Glioma Cell Lines Exposed To Radiation At Genomic Level And An Evidence From Interaction Between Apoptosis And Autophagy

Tumor recurrence after radiotherapy of glioma due to radio-resistant nature ofglioma tumor cells is among the major challenges for radiobiology that require morefocused research. Particularly mutant of glial cells and blood brain barrier that blockthe passage of immune cells and small therapeutic molecule is among the major factorthat make glioma therapy more challenging. Therefore in case of glioma therapy theselection of therapy have to choose very carefully. In this study to accomplish theglioma therapy enhancement we apply various doses of radiation to estimate the radiotolerance of glioma to interpret radio resistance mechanism. We chose rationalmethod to estimate the glioma cell loss at different doses of radiation. Moreover, it isnecessary to reduce damage to normal surrounding tissues while targeting the gliomatumor with radiation to improve the survival rate of patients affected with gliomatumor. To date plenty of researchers based on genome comparison have described thatradio-resistance of glioma might be due to DNA repair; cell cycle as well as DNAreplication’s protein interaction. However apoptosis and necrosis are main mechanisminvolved in cell loss after radiotherapy. In glioma U87, which has an advantage inbeing radiation resistant,mechanisms of DNA repair and complete cell cycleregulation apoptosis and necrosis are the main mechanism that involved in radiationtolerance of glioma tumor cells. U87,which has an advantage in radiationresistant,mechanisms of DNA repair and complete cell cycle regulation triggers theradiation tolerance of cells. As for glioma SF767with high sensitivity of radiation,DNA replication and the lack of cell cycle regulation mode change caused a large number of apoptotic cells after radiation. However in glioma U251, lack of DNArepair mechanisms decreased radiation tolerance, but the mechanism of cell cycleregulation prevent the cells apoptosis，therefore it maintain constant cell number andno significant increase observed in cell proliferation.By analyzing the maintenance ofcell number related apoptosis gene, we found that apoptosis promoting gene inU251cells expressed in the early hours of U87and SF767, apoptotic inhibiting geneoccurred jointly post radiation exposure. However, pro apoptotic genes and apoptosisinhibiting gene in U87and SF767simultaneously expressed in the late hours ofradiation exposure.The analysis of transcriptional regulation of apoptotic genemanifest that transcription of the U251and U87’s gene is directly related to regulationof the protein P53’s transcription factor. This factor suggestP53as transcription factoris vital for gene regulation mechanism after radiotherapy of nerve glioma cells.We found that after radiation P53protein was regulated by the nucleotidesequence of the promoter region and the expression level of P53transcriptioncomplex protein. Moreover, differences in transcription factor of P53among threekinds of glioma cells line determine the difference in cell radio sensitivity. In U87after irradiation, P53gene regulates both cell apoptosis and retardant of cell cycle,which provides repair time for DNA. Meanwhile, other transcription factors of P53like MDM2, act as a counter-regulation role of P53levels, which leads to senescenceand death of tumor cells. After radiation of the U251, mutations of P53causesincrease in P53expression and the loss of degradation mechanism. P53promote highexpression of pro-apoptotic gene. Moreover, as a transcription factor, the transcriptional regulation of cell cycle related to P53genes induces cell fall into along-time retardarce, and then the cell gets into senescence.But for theradiation-sensitive cells like SF767, there was no prominent changes in P53expression levels were observed. Moreover, transcriptional regulation of cell cyclerelated genes of P53has not changed significantly that ultimately cause apoptosis.However, In the glioma cells of U87and U251,the variable expression level of theP53gene transcription complex protein triggers significantdifferences in the numberof P53transcriptional gene. After radiation,the expression level of constitutiveprotein in U251did not change significantly, therefore the transcription rate is lowerin u251as compare to U87.In order to increase the radio-sensitivity of the glioma cells, We studied therelationship between aggregation of misfolded proteins and DNA damage associatedwith reference to autophagy and apoptosis after radiation. We observed different modeof cell death after glioma cell radiation and enrichment of DR5gene regulatorypathways. while in different glioma cell autophagy potentially occurs, through theautophagy-related proteins found in different glue P62protein terms of the degree ofintensity of autophagy stromal tumor cells plays an important functional role. theregulatory protein mTOR protein autophagy inhibition of autophagy has a function,which in addition to the ATG13-ATG1-ULK1complex interrelated inhibition, but alsowith the P62protein degradation pathway for the degree of inhibition was directlylinked. We found that autophagy in glioma cells after irradiation by apoptosis proteinactivity caspase8of LC3B to promote the role and promote apoptosis through DR5on apoptosis regulatory pathways, and interactions of regulatory networks in patients theprimary cells also play a key role in regulating the treatment of glioma tumor targetsprovided adoptable.In this paper, we discussed different glioma cell radiation sensitivity andapoptotic mechanism of autophagy depth. Our study indicates that in differentradio-resistant glioma cells exhibit significant differences, in P53pathways andtranscriptional regulation of autophagy and apoptosis. This feature can provide tworeliable treatment options of glioma treatment.