1.Demethylzeylasteral inhibits proliferation,migration and invasion and promotes apoptosis of non-small cell lung cancer cells by inhibiting the AKT/CREB signaling pathway
Qiqi HAN ; Mengran YE ; Qili JIN
Journal of Southern Medical University 2024;44(2):280-288
Objective To investigate the mechanism underlying the inhibitory effects of Demethylzeylasteral(T-96)on non-small cell lung cancer(NSCLC)cells.Methods We first examined the effects of different concentrations(1,3,10,and 30 μmol/L)of demethylzeylasteral on morphology and cell number of A549 and H1299 cells.The changes in proliferation,cell viability,migration,invasion,and apoptosis of A549 and H1299 cells following demethylzeylasteral treatment were detected using clone formation,CCK-8,cell scratch,Transwell,and flow cytometric assays,and the effect of SC79 treatment against demethylzeylasteral-induced cell apoptosis was assessed.Western blotting was performed to detect the changes in expressions of E-cadherin,N-cadherin,vimentin,Bax,Bcl-2 and cleaved caspase-3 and phosphorylation of AKT/CREB in demethylzeylasteral-treated A549 and H1299 cells and the cellular expressions of apoptotic proteins following treatment with both demethylzeylasteral and SC79.Results T-96 treatment caused elongation of the cell body and widening of the intercellular space and significantly inhibited cell viability,proliferation,migration and invasion of A549 and H1299 cells(P<0.05).Flow cytometry showed that demethylzeylasteral induced apoptosis in both A549 and H1299 cells,whereas SC79 treatment obviously attenuated its pro-apoptotic effect(P<0.05).Western blotting revealed up-regulated expressions of Bax and cleaved caspase-3 proteins and lowered Bcl-2 expression level in demethylzeylasteral-treated A549 and H1299 cells,but co-treatment with SC79 obviously attenuated the expressions of the apoptotic proteins.T-96 significantly up-regulated the expression level of E-cadherin,down-regulated the expressions of N-cadherin and vimentin,and inhibited the phosphorylation of AKT and CREB in the two cell lines(P<0.05).Conclusion T-96 inhibits the proliferation,migration and invasion and induces apoptosis of NSCLC cells possibly by inhibiting the AKT/CREB signaling pathway.
2.Demethylzeylasteral inhibits proliferation,migration and invasion and promotes apoptosis of non-small cell lung cancer cells by inhibiting the AKT/CREB signaling pathway
Qiqi HAN ; Mengran YE ; Qili JIN
Journal of Southern Medical University 2024;44(2):280-288
Objective To investigate the mechanism underlying the inhibitory effects of Demethylzeylasteral(T-96)on non-small cell lung cancer(NSCLC)cells.Methods We first examined the effects of different concentrations(1,3,10,and 30 μmol/L)of demethylzeylasteral on morphology and cell number of A549 and H1299 cells.The changes in proliferation,cell viability,migration,invasion,and apoptosis of A549 and H1299 cells following demethylzeylasteral treatment were detected using clone formation,CCK-8,cell scratch,Transwell,and flow cytometric assays,and the effect of SC79 treatment against demethylzeylasteral-induced cell apoptosis was assessed.Western blotting was performed to detect the changes in expressions of E-cadherin,N-cadherin,vimentin,Bax,Bcl-2 and cleaved caspase-3 and phosphorylation of AKT/CREB in demethylzeylasteral-treated A549 and H1299 cells and the cellular expressions of apoptotic proteins following treatment with both demethylzeylasteral and SC79.Results T-96 treatment caused elongation of the cell body and widening of the intercellular space and significantly inhibited cell viability,proliferation,migration and invasion of A549 and H1299 cells(P<0.05).Flow cytometry showed that demethylzeylasteral induced apoptosis in both A549 and H1299 cells,whereas SC79 treatment obviously attenuated its pro-apoptotic effect(P<0.05).Western blotting revealed up-regulated expressions of Bax and cleaved caspase-3 proteins and lowered Bcl-2 expression level in demethylzeylasteral-treated A549 and H1299 cells,but co-treatment with SC79 obviously attenuated the expressions of the apoptotic proteins.T-96 significantly up-regulated the expression level of E-cadherin,down-regulated the expressions of N-cadherin and vimentin,and inhibited the phosphorylation of AKT and CREB in the two cell lines(P<0.05).Conclusion T-96 inhibits the proliferation,migration and invasion and induces apoptosis of NSCLC cells possibly by inhibiting the AKT/CREB signaling pathway.
3. Research progress of thyroid dysfunctions during treatment with immune-checkpoint inhibitors
Hang MIN ; Mengran GUO ; Yue YE ; Xiaoshuang XU ; Hang MIN ; Mengran GUO ; Yue YE ; Xiaoshuang XU ; Donghu ZHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(2):223-229
Thyroid dysfunction (TD) is one of the commonest endocrine immunotherapy-related adverse events (IRAEs) during cancer patients' treatment with immune checkpoint inhibitors (ICIs). In the hope that cooperation between departments will be enhanced to alleviate the side effect of immunotherapy which thyroid dysfunctions can cause, this review is contributed to make more endocrinologists and oncologists acknowledge and master clinical characteristics, diagnostic methods and therapeutic strategies of thyroid IRAEs, by the introduction of its pathogenesis, epidemiological features, diagnosis, treatment and prognosis.
4.Association analysis of various obesity-related indices and vitamin D deficiency in middle-aged and elderly population in Lanzhou
Hang MIN ; Fang YANG ; Donghu ZHEN ; Xulei TANG ; Hongxia CHE ; Conghui GUAN ; Nan ZHAO ; Lijuan LIU ; Jie HAN ; Yue YE ; Mengran GUO ; Xiaoshuang XU
Chinese Journal of Clinical Nutrition 2023;31(1):1-8
Objective:To analyze and compare the association between different obesity-related indices and vitamin D deficiency in middle-aged and elderly population dwelled in Lanzhou city.Methods:From May, 2011 to September, 2012, middle-aged and elderly individuals with complete baseline data were included via randomly cluster sampling from 3 communities in Lanzhou. The subjects were divided into 4 subgroups by vitamin D levels and various obesity-related indices were compared across subgroups with the same gender. The relationship between the obesity-related indices and the severity of vitamin D deficiency was analyzed using Spearman correlation analysis, and the effects of different obesity-related indices on the severity of vitamin D deficiency was analyzed using multivariate logistic regression analysis.Results:A total of 9 437 residents were included. The overall prevalence of vitamin D deficiency was 97.7%. Compared with the group with lower vitamin D level, participants in the group with higher vitamin D level showed evidently lower body mass index (BMI), waist circumference (WC), lipid accumulation product (LAP), visceral adiposity index (VAI) and triglyceride/ high density lipoprotein cholesterol (TG/HDL-C) ratio in the total population and females, while only WC, LAP, VAI and TG/HDL-C in the males (all P<0.05). Spearman correlation analysis showed that BMI, WC, LAP, VAI and TG/HDL-C were positively correlated with the severity of vitamin D deficiency in the total population and the females, while only LAP, VAI and TG/HDL-C in the males (all P<0.05) . Multivariate logistic regression analysis showed that higher levels of these obesity related indices were correlated with more severe vitamin D deficiency in the total population and the females, while only higher LAP, VAI and TG/HDL-C in the males (all P<0.05). The effects of higher LAP was the most prominant in the total population ,the females and the males. Conclusion:Various obesity phenotypes are closely related to vitamin D deficiency in middle-aged and elderly women, while only visceral obesity and abnormal lipid metabolism are related to vitamin D deficiency in middle-aged and elderly men, with LAP being the most important influencing factor.