Atractylon Inhibits The Tumorigenesis Of Glioblastoma Through SIRT3 Signaling

Background:Glioblastoma(GBM)is an aggressive brain tumor that accounts for about 40-50% of all primary intracranial tumors and originates from the neuroepithelium.The annual incidence of glioma in China is about 50,000-80,000 of 100,000 people.At present,the main treatment methods for glioma still rely on surgery,radiotherapy and postoperative adjuvant chemotherapy.However,glioblastoma tumor cells can infiltrate into normal brain tissue which caused the prognosis for GBM patients is unsatisfactory.At the same time,due to the complicated immune resistance mechanism of current treatment means,although traditional treatment can extend the life span of patients with GBM,the quality of life of patients after treatment is reduced,and the survival rate is often short.Therefore,in order to improve the survival rate of patients with GBM,it is necessary to adopt new personalized treatment plans,such as targeted therapy,immunotherapy,traditional Chinese medicine therapy and other ways.Atractylon is a sesquiterpenoid compound isolated from Atractylodes lancea(Thunb.)DC.or Atractylodes chinensis(DC.)Koidz,which has a long history in China.Modern pharmacological studies have found that atractylon can be used to treat rheumatic diseases,digestive diseases,liver protection and influenza.In recent years,studies have reported that atractylon also has anti-inflammatory,anti-nociceptive,antiviral,anti-ulcer and anti-tumor effects.However,whether atractylon has anti-glioma effects remains unclear.Objective:(1)To clarify the inhibitory effect of atractylon on proliferation,migration and apoptosis of glioblastoma;(2)To elucidate the molecular mechanism of atractylon inhibiting the proliferation,migration and promoting apoptosis of glioblastoma;(3)To clarify the clinical significance of atractylon in the treatment of glioblastoma in vivo.Methods:(1)The effects of atractylon on the proliferation and migration of glioma cells were detected by CCK8 assay,cell colony assay,PH3 immunofluorescent assay,wound-healing assay and transwell assay;(2)The effect of atractylon on apoptosis of glioma cells were detected by flow cytometry,PI staining and western blotting;(3)The expression of SIRT3 in glioma cells treated with atractylon was detected by western blot combined with immunofluorescence staining and RT-PCR.(4)The effect of SIRT3 on anti-GBM of atractylon was studied by using SIRT3 inhibitor 3-TYP;(5)The anti-GBM effect of atractylon in vivo was studied by subcutaneous tumor formation experiment in nude mice.Results:(1)The results of CCK8 assay,cell colony assay and PH3 immunofluorescent showed that atractylon could inhibit GBM cell proliferation;Wound-healing assay and transwell assay showed that atractylon could inhibit the migration of GBM cells.(2)Flow cytometry showed that atractylon caused G1 cell arrest and induced apoptosis in GBM cells;PI staining and western blotting showed that atractylon could induce apoptosis.(3)Western blotting,immunofluorescent staining and RT-PCR showed that SIRT3 expression was upregulated in GBM cells treated with atractylon.(4)SIRT3 inhibitor 3-TYP could reverse the growth of GBM inhibited by atractylon.(5)The results of subcutaneous tumor formation in nude mice showed that atractylon could play an anti-GBM role in vivo and had little toxic and side effects on various organs.Conclusion:Atractylon inhibited the growth of GBM by upregulating SIRT3,which inhibited the proliferation and migration of GBM and induced apoptosis of GBM in vitro and in vivo.This thesis reveals the effect and mechanism of atractylon on GBM,which is very important for the treatment of GBM and has great significance.