摘要
目的探讨绞股蓝皂苷LI(Gypenoside LI)通过调控脂质酸代谢通路中的关键酶——肉碱棕榈酰转移酶1B(CPT1B)来抑制结肠癌生长的作用机制。方法通过体外实验,采用不同浓度的Gypenoside LI干预结肠癌RKO和SW620细胞,并通过CCK-8法、细胞划痕实验、细胞克隆实验以及细胞活死染色等方法,全面评估了Gypenoside LI对细胞增殖、迁移及凋亡的影响。同时,利用人结肠癌组织微阵列芯片(TMA),结合多重荧光免疫组化技术,分析了CPT1B在结肠癌及癌旁组织中的表达情况。siRNA转染SW620细胞,运用荧光定量PCR(qPCR)和Western blot检测siRNA转染后的CPT1B的mRNA和蛋白表达水平。此外,通过体内实验建立了裸鼠结肠癌模型,探讨了Gypenoside LI对结肠癌生长的抑制作用。结果体外实验表明,Gypenoside LI能有效抑制RKO和SW620细胞的增殖和迁移(P<0.05,P<0.001),且呈现浓度和时间依赖性。此外,通过多重荧光免疫组化技术发现,CPT1B在结肠癌组织中的表达水平显著高于癌旁组织,而Gypenoside LI通过抑制CPT1B,促进ROS堆积(P<0.001),体内实验进一步证实,Gypenoside LI能够抑制裸鼠结肠癌的生成,并降低CPT1B的表达(P<0.001)。结论本研究揭示了Gypenoside LI通过下调CPT1B抑制结肠癌生长的机制,增加活性氧类(ROS)的堆积,引起脂肪酸氧化代谢的障碍,最终导致结肠癌细胞凋亡,这些发现为结肠癌的治疗提供了新的思路和潜在的药物靶点。
Objective To elucidate the mechanism through which Gypenoside L inhibits the growth of colon cancer by modulating carnitine palmitoyltransferase 1B(CPT1B),a pivotal enzyme in the fatty acid metabolism pathway.Methods Through in vitro experiments,various concentrations of Gypenoside LI LI were applied to inter‐vene in colon cancer RKO and SW620 cells.The effects of Gypenoside LI on these cells were comprehensively evalu‐ated using the CCK‐8 assay,wound healing assay,colony formation assay,and live‐dead cell staining,focusing on its impact on cell proliferation,migration,and apoptosis.Additionally,a human colon cancer tissue microarray(TMA)was utilized in conjunction with multiplex fluorescence immunohistochemistry to analyze the expression of CPT1B in colon cancer and adjacent tissues.SW620 cells were transfected with siRNA,and the mRNA and protein expression levels of CPT1B post‐transfection were assessed using quantitative real‐time PCR(qPCR)and Western blotting.Furthermore,an in vivo nude mouse colon cancer model was established to investigate the inhibitory effect of Gypenoside LI LI on colon cancer growth.Results In vitro experiments demonstrated that Gypenoside LI LI effectively inhibited the proliferation and migration of RKO and SW620 cells in a concentration‐and time‐dependent manner.Additionally,multiple fluorescence immunohistochemistry analyses revealed that the expression level of CPT1B in colon cancer tissues was significantly higher than that in adjacent non‐tumor tissues.Gypenoside LI LI promoted ROS accumulation by inhibiting CPT1B expression.In vivo experiments further confirmed that Gypenoside LI LI could inhibit tumor formation in nude mice and reduce CPT1B expression.Conclusions This study elucidates the mechanism by which Gypenoside LI inhibits the growth of colon cancer cells.Specifically,it downregulates CPT1B,leading to increased accumulation of reactive oxygen species(ROS),disruption of fatty acid oxidation metabolism,and ultimately inducing apoptosis in colon cancer cells.These findings offer valuable insights into colon cancer treatment,suggesting new therapeutic strategies and potential drug targets.
作者
朱文宇
张红卫
唐德才
陈芳园
蒋华
闵海燕
丁洁
ZHU Wenyu;ZHANG Hongwei;TANG Decai;CHEN Fangyuan;JIANG Hua;MIN Haiyan;DING Jie(Department of Cancer Center,the Third Affiliated Hospital of Nanjing Medical University,Changzhou Second People′s Hospital,Changzhou 213000,Jiangsu,China;不详)
出处
《实用医学杂志》
北大核心
2025年第2期162-169,共8页
The Journal of Practical Medicine
基金
国家自然科学基金青年基金资助项目(编号:82303960)
常州卫健委科技基金资助项目(编号:QN202320)
南京医科大学常州医学中心基础研究项目(编号:CMCC202307)。
