目的探讨斑蝥素(Cantharidin)对结直肠癌SW480细胞增殖、侵袭及凋亡的影响,并初步阐明其潜在分子机制。方法采用体外培养的SW480细胞,通过MTS法和克隆形成实验检测细胞活力与长期增殖能力;利用Transwell实验评估细胞侵袭能力;运用流式...目的探讨斑蝥素(Cantharidin)对结直肠癌SW480细胞增殖、侵袭及凋亡的影响,并初步阐明其潜在分子机制。方法采用体外培养的SW480细胞,通过MTS法和克隆形成实验检测细胞活力与长期增殖能力;利用Transwell实验评估细胞侵袭能力;运用流式细胞术分析细胞凋亡与周期分布;并采用Western Blot技术检测PI3K/AKT信号通路关键蛋白的表达及其磷酸化水平。结果与对照组相比,斑蝥素能够剂量依赖性地显著抑制SW480细胞的增殖(48 h IC50为11.63μM)、克隆形成及侵袭能力。此外,斑蝥素可诱导细胞周期阻滞于G2/M期,并显著促进细胞凋亡。研究表明,斑蝥素处理能显著抑制PI3K与AKT的磷酸化,下调总PI3K、总AKT、CDK4、MMP9及抗凋亡蛋白Bcl-2的表达,同时上调促凋亡蛋白Bax的表达。结论斑蝥素可通过抑制PI3K/AKT信号通路,进而抑制结直肠癌SW480细胞的增殖与侵袭,并诱导其凋亡。展开更多
Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,...Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,and the rats received oral CSⅣor atorvastatin.The body weight,organ weights,food intake,calorie intake,lipid parameters,3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)/mevalonate ratio,collagen,free fatty acid,cardiac parameters,apolipoprotein(A and B),antioxidant parameters,inflammatory cytokines,and inflammatory parameters were assessed.The mRNA expressions of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),IL-6,IL-17,PI3K,AKT,and mTOR were estimated.Results:CSⅣsignificantly modulated food intake,body weight,organ weight(liver,kidney,and heart),and calories(P<0.05).Total cholesterol,triglycerides,very low-density lipoprotein cholesterol,low-density lipoprotein cholesterol,cardiovascular risk index-1,and cardiovascular risk index-2 were decreased,while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSⅣgroup(P<0.05).Besides,CSⅣsignificantly restored the level of HMG-CoA/mevalonate ratio,collagen,free fatty acid,cardiac parameters(creatinine kinase-MB,lactate dehydrogenase,cTnT,cTnI),apolipoprotein(apolipoprotein A and apolipoprotein B),antioxidant parameters(MDA,CAT,GPx,GSH,SOD),inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10),inflammatory parameters(COX-2,TGF-β,NF-κB),intercellular adhesion molecule-1,vascular cell adhesion molecule-1,and monocyte chemoattractant protein-1.CSⅣalso decreased the mRNA expression of IL-1β,TNF-α,IL-6,IL-17,PI3K,AKT,and mTOR.Conclusions:This study showed the anti-atherosclerosis effect of CSⅣagainst high-fat diet-induced atherosclerosis in rats via alteration of NF-κB/COX-2 and PI3K/AKT/mTOR signaling pathway.展开更多
文摘目的探讨斑蝥素(Cantharidin)对结直肠癌SW480细胞增殖、侵袭及凋亡的影响,并初步阐明其潜在分子机制。方法采用体外培养的SW480细胞,通过MTS法和克隆形成实验检测细胞活力与长期增殖能力;利用Transwell实验评估细胞侵袭能力;运用流式细胞术分析细胞凋亡与周期分布;并采用Western Blot技术检测PI3K/AKT信号通路关键蛋白的表达及其磷酸化水平。结果与对照组相比,斑蝥素能够剂量依赖性地显著抑制SW480细胞的增殖(48 h IC50为11.63μM)、克隆形成及侵袭能力。此外,斑蝥素可诱导细胞周期阻滞于G2/M期,并显著促进细胞凋亡。研究表明,斑蝥素处理能显著抑制PI3K与AKT的磷酸化,下调总PI3K、总AKT、CDK4、MMP9及抗凋亡蛋白Bcl-2的表达,同时上调促凋亡蛋白Bax的表达。结论斑蝥素可通过抑制PI3K/AKT信号通路,进而抑制结直肠癌SW480细胞的增殖与侵袭,并诱导其凋亡。
基金funded by the Yancheng Municipal Health Commission 2024 Medical Research Project(YK2024166).
文摘Objective:To investigate the anti-atherosclerosis effect of chikusetsusaponinⅣ(CSⅣ)against high-fat diet-induced atherosclerosis in rats.Methods:A high-fat diet was used for the induction of atherosclerosis in rats,and the rats received oral CSⅣor atorvastatin.The body weight,organ weights,food intake,calorie intake,lipid parameters,3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)/mevalonate ratio,collagen,free fatty acid,cardiac parameters,apolipoprotein(A and B),antioxidant parameters,inflammatory cytokines,and inflammatory parameters were assessed.The mRNA expressions of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),IL-6,IL-17,PI3K,AKT,and mTOR were estimated.Results:CSⅣsignificantly modulated food intake,body weight,organ weight(liver,kidney,and heart),and calories(P<0.05).Total cholesterol,triglycerides,very low-density lipoprotein cholesterol,low-density lipoprotein cholesterol,cardiovascular risk index-1,and cardiovascular risk index-2 were decreased,while high-density lipoprotein cholesterol and anti-atherogenic index were increased significantly in the CSⅣgroup(P<0.05).Besides,CSⅣsignificantly restored the level of HMG-CoA/mevalonate ratio,collagen,free fatty acid,cardiac parameters(creatinine kinase-MB,lactate dehydrogenase,cTnT,cTnI),apolipoprotein(apolipoprotein A and apolipoprotein B),antioxidant parameters(MDA,CAT,GPx,GSH,SOD),inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10),inflammatory parameters(COX-2,TGF-β,NF-κB),intercellular adhesion molecule-1,vascular cell adhesion molecule-1,and monocyte chemoattractant protein-1.CSⅣalso decreased the mRNA expression of IL-1β,TNF-α,IL-6,IL-17,PI3K,AKT,and mTOR.Conclusions:This study showed the anti-atherosclerosis effect of CSⅣagainst high-fat diet-induced atherosclerosis in rats via alteration of NF-κB/COX-2 and PI3K/AKT/mTOR signaling pathway.