Effect Of Abnormal Glucose Metabolism On Papillary Thyroid Cancer And Its Mechanism

Part 1 Correlation between Components of Metabolic Syndrome and Papillary Thyroid Cancer in Thyroid NodulesObjective To investigate the correlation between metabolic syndrome components and papillary thyroid carcinoma in thyroid nodules.Methods A retrospective analysis was used to analyze 495 cases diagnosed with thyroid nodules and received thyroid fine needle aspiration biopsy(FNAB).According to FNAB and surgical biopsy results,ten cases of follicular carcinoma,one case of medullary carcinoma and one case of lymphoma were excluded,the patients were divided into thyroid papillary cancer group(n=102)And benign nodules group(n=381),the differences between the two groups of basic data,metabolic syndrome components,thyroid function related indicators were compared.Results The body mass index(BMI),fasting blood glucose(FBG),serum glycerin trilaurate(TG)and thyroid stimulating hormone(TSH)of thyroid papillary carcinoma were significantly higher than those of benign nodules(all p<0.05).Gender,systolic blood pressure(SBP),Diastolic blood pressure(DBP),serum total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),free triiodothyronine3(FT3),free thyroxine4(FT4),anti-thyroid stimulating hormone receptor antibody(TRAb),anti-thyroid peroxidase antibody(TPOAb),and anti-thyroglobulin antibody(TGAb)were no significant changes(p>0.05).Further logistic regression analysis found that BMI(OR=1.61,95%CI: 1.25 ~ 2.17),FBG(ORabnormal glucose tolerance=1.31,95%CI: 1.15~1.97;ORdiabetes=1.37,95%CI: 1.09~1.85)、TSH(OR=1.12,95%CI: 1.05~1.94),age(OR=0.87,95%CI:0.82~0.97)are independent risk factors for PTC in thyroid nodules,there was no correlation between TG and PTC.Conclusion Metabolic syndrome components BMI and FBG are independent risk factors for PTC in thyroid nodules.Age is negatively correlated with PTC,and TSH is positively correlated with PTC.Part 2 Effect of PI3K/Akt/Nrf2 Signaling Pathway on Proliferation and Apoptosis of Papillary Thyroid Cancer K1 Cells underHigh Glucose Environmental ConditionsObjective To investigate the effects of PI3K/Akt/Nrf2 signaling pathway on proliferation and apoptosis of human papillary thyroid carcinoma K1 cells under high glucose environmental conditions,and explore the role of glucose metabolism-related enzymes,oxidative stress and apoptosis-related proteins in the proliferation and apoptosis of K1 cells.Methods According to different treatment factors,K1 cells were divided into four groups: control group(5.5mmol/L glucose cultured for 24 h,then 25mmol/L glucose cultured for 24h),Nrf2-siRNA group(transfected cells in 5.5mmol/L glucose for24 h,then cultured in 25mmol/L glucose for 24h),Nc-siRNA group(negativly transfected cells for 24 h under 5.5mmol/L glucose conditions,then cultured in 25mmol/L glucose for 24h),LY294002 group(negativly transfected cells for 24 h under 5.5mmol/L glucose conditions,plus 50umol/L LY294002pre-incubation for 0.5h and then cultured in 25mmol/L glucose for 24h).Cell proliferation was detected by MTT assay,apoptosis was detected by flow cytometry,Nrf2 mRNA expression was detected by RT-PCR,and the expression levels of PI3 K,p-PI3 K,Akt,p-Akt,Nrf2(nuclear and cytoplasmic protein),G6 PD,PKM2,Bcl-2 and Caspase-3 proteins were detected by Western blot.ROS was detected by chemiluminescence method,GSH-Px content was detected by colorimetry,and SOD activity was detected by WST-1 method.Results Compared with the control group,nuclear protein,cytoplasmic protein,and nuclear plasma protein ratio of Nrf2 were significantly inhibited in Nrf2-siRNA group(all p <0.01),there was no significant change in Nc-siRNA group(all p>0.05),the proliferation rate of K1 cells in Nrf2-siRNA group was significantly decreased,and the protein expression of G6 PD and PKM2 were down-regulated(all p<0.05),the proliferation rate,protein expression of G6 PD and PKM2 in Nc-siRNA group did not change(all p>0.05).Compared with the control group,the early apoptosis rate and late apoptotic rate of K1 cells in Nrf2 siRNA group were significantly increased(all p<0.01),the levels of ROS and Caspase-3 were significantly increased,and GSH-Px,SOD and Bcl-2 were significantly decreased(all p<0.01).There was no significant change in the levels of ROS,GSH-Px,SOD,Caspase-3 and Bcl-2 in Nc-siRNA group(all p>0.05).Compared with the control group,the total protein PI3 K and Akt levels of K1 cells in LY294002 group were not significantly changed(all p>0.05),p-PI3 K,p-Akt,nuclear Nrf2,Nrf2 cytoplasmic protein levels were significantly inhibited(all p<0.01).Conclusion High glucose can activate PI3K/Akt signaling pathway to regulate Nrf2 expression and nuclear translocation.It may promote K1 cell proliferation by up-regulating the expression of PKM2 and G6 PD,inhibit K1 cell apoptosis by down-regulating the level of oxidative stress and Caspase-3expression,up-regulating the expression of Bcl-2.