贝母素乙通过下调CDK2/CDK4/CDK6和cyclin D1表达抑制人结肠腺癌SW480细胞活力
Peiminine inhibits viability of human colonic adenocarcinoma SW480 cells by down-regulating expression of CDK2/CDK4/CDK6 and cyclin D1
杨霞 1李雅茹 1李玥 2毛泓月 3白冰 2李一权 2韩继成 2万怡宁 2谢诗敏 2朱羿龙 4金宁一5
作者信息
- 1. 延边大学医学院病理学与病理生理学教研室,吉林 延吉 136200
- 2. 长春中医药大学院士工作室,吉林 长春 130117
- 3. 中国农业科学研究院长春兽医研究所,吉林 长春 130122
- 4. 长春中医药大学院士工作室,吉林 长春 130117;中国农业科学研究院长春兽医研究所,吉林 长春 130122
- 5. 延边大学医学院病理学与病理生理学教研室,吉林 延吉 136200;中国农业科学研究院长春兽医研究所,吉林 长春 130122
- 折叠
摘要
目的:探究贝母素乙(peiminine)对人结肠腺癌细胞(SW480)活力、迁移和侵袭的抑制作用并探讨其抑制SW480增殖的作用机制.方法:用不同剂量的贝母素乙处理人结肠腺癌细胞SW480和人正常结肠上皮细胞CCD-841CoN,通过CCK-8实验确定贝母素乙抑制SW480活力的最适剂量和最佳作用时间;划痕和Transwell实验检测贝母素乙对SW480迁移与侵袭能力的影响;流式细胞术和Western blot检测贝母素乙对SW480细胞周期及细胞周期相关蛋白表达的影响;构建SW480移植瘤裸鼠模型,在体内分析贝母素乙对SW480活力及细胞周期相关蛋白表达的影响.结果:与对照组相比,当贝母素乙作用浓度为110 mg/L时能够显著抑制SW480细胞活力、迁移和侵袭能力(P<0.01),并诱导SW480细胞周期G1期阻滞,周期相关蛋白细胞周期蛋白依赖性激酶2(CDK2)、CDK4、CDK6、细胞周期蛋白D1(cyclin D1)、p-Rb/Rb、E2F1、E2F3和E2F4的表达水平受到显著抑制(P<0.05);在体内,贝母素乙抑制SW480移植瘤的活力、延长荷瘤裸鼠的生存周期,影响肿瘤组织中CDK2、CDK4、CDK6和cyclin D1的表达.结论:贝母素乙通过下调CDK2、CDK4、CDK6和cyclin D1的表达,引起SW480细胞的G1期阻滞,进而抑制人结肠腺癌细胞SW480增殖.
Abstract
AIM:This study examined the inhibitory effect of peiminine on the human colonic adenocarcino-ma cell line SW480 and explored the underlying mechanisms.METHODS:SW480 and human normal colonic epithelial CCD-841CoN cells were treated with different concentrations of peiminine and subjected to the CCK-8 assay to select the optimal treatment time and concentration of the compound.SW480 cell migration and invasion were evaluated by the wound-healing and Transwell assays.Cell cycle progression was analyzed by flow cytometry.The expression levels of cell cycle-related proteins were examined by Western blot.SW480 xenograft tumor model was established in nude mice to ex-amine the effect of peiminine on tumor growth and the expression of cell cycle-related proteins in vivo.RESULTS:Peimi-nine(110 mg/L)significantly inhibited the proliferation of SW480 cells compared with the control group(P<0.01),caused cell cycle arrest at G1 phase,and significantly downregulated the expression of cyclin dependent kinase 2(CDK2),CDK4,CDK6,cyclin D1,p-Rb/Rb,E2F1,E2F3,and E2F4(P<0.05).Peiminine inhibited SW480 xenograft tumor growth,prolonged the survival of model mice,and affected the expression of CDK2,CDK4,CDK6,and cyclin D1 in tu-mor tissues.CONCLUSION:Peiminine promotes G1 phase arrest by down-regulating the expression of CDK2,CDK4,CDK6,and cyclin D1,thereby inhibiting the proliferation of SW480 cells.
关键词
SW480细胞/贝母素乙/周期蛋白依赖性激酶/细胞周期Key words
SW480 cells/peiminine/cyclin-dependent kinases/cell cycle引用本文复制引用
基金项目
吉林省自然科学基金(YDZJ202401687ZYT)
吉林省中医药科技项目(2024255)
吉林省科技发展计划(20220508075RC)
出版年
2024
国家科技期刊平台
NSTL
万方数据