Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell...Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.展开更多
目的:探讨姜黄素抗C57BL/6小鼠肺纤维化分子机制。方法:博来霉素气管注射造小鼠肺纤维化模型,随机分组:对照组(气管内注入0.1mL生理盐水),模型组(气管内注入0.025U博来霉素),姜黄素组(气管内注入0.025U博来霉素);造模第2天,对照组和模...目的:探讨姜黄素抗C57BL/6小鼠肺纤维化分子机制。方法:博来霉素气管注射造小鼠肺纤维化模型,随机分组:对照组(气管内注入0.1mL生理盐水),模型组(气管内注入0.025U博来霉素),姜黄素组(气管内注入0.025U博来霉素);造模第2天,对照组和模型组给予生理盐水灌胃,姜黄素组给予200mg/kg/d姜黄素灌胃,分别于造模后第7、14、28天取材。采用Mallory染色观察肺组织胶原表达变化;应用免疫组化检测Cathepsin K蛋白的表达,经图像分析各组之间的差异;在免疫组化的基础上,Re-al Time RT-PCR,Western-blot进一步验证Cathepsin K mRNA及蛋白在各组之间表达的差异。结果:Mallory染色结果显示姜黄素组、模型组与对照组比较胶原表达都比对照组高,姜黄素组与模型组比较胶原表达减少;姜黄素组、模型组与对照组比较,Cathepsin K表达都有不同程度增加;但姜黄素组与模型组比较Cathepsin K蛋白表达显著增加,其中第14天(P=0.006);第7天(P=0.015);28天(P=0.027);Real Time RT-PCR分析CathepsinK mRNA表达,姜黄素组与模型组进行比较发现,姜黄素组比模型组明显增加,第7天(P=0.047),第14天(P=0.001),第28天增加不明显(P=0.053)。结论:姜黄素通过增加Cathepsin K的表达从而降解胶原而实现抗纤维化作用。展开更多
基金supported by Natural Science Foundation of Hunan Province(No.2023JJ40511)Excellent Youth Project of Scientific Research Program of Hunan Education Department(No.22B0370)+2 种基金Project of Traditional Chinese Medicine Administration of Hunan Province(No.B2023034)Science and Technology Development Foundation of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University(No.LYYB202214)Hunan Provincial Hygiene and Health Commission Health Research Project(No.W20243165).
文摘Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.
文摘目的:探讨姜黄素抗C57BL/6小鼠肺纤维化分子机制。方法:博来霉素气管注射造小鼠肺纤维化模型,随机分组:对照组(气管内注入0.1mL生理盐水),模型组(气管内注入0.025U博来霉素),姜黄素组(气管内注入0.025U博来霉素);造模第2天,对照组和模型组给予生理盐水灌胃,姜黄素组给予200mg/kg/d姜黄素灌胃,分别于造模后第7、14、28天取材。采用Mallory染色观察肺组织胶原表达变化;应用免疫组化检测Cathepsin K蛋白的表达,经图像分析各组之间的差异;在免疫组化的基础上,Re-al Time RT-PCR,Western-blot进一步验证Cathepsin K mRNA及蛋白在各组之间表达的差异。结果:Mallory染色结果显示姜黄素组、模型组与对照组比较胶原表达都比对照组高,姜黄素组与模型组比较胶原表达减少;姜黄素组、模型组与对照组比较,Cathepsin K表达都有不同程度增加;但姜黄素组与模型组比较Cathepsin K蛋白表达显著增加,其中第14天(P=0.006);第7天(P=0.015);28天(P=0.027);Real Time RT-PCR分析CathepsinK mRNA表达,姜黄素组与模型组进行比较发现,姜黄素组比模型组明显增加,第7天(P=0.047),第14天(P=0.001),第28天增加不明显(P=0.053)。结论:姜黄素通过增加Cathepsin K的表达从而降解胶原而实现抗纤维化作用。
