中药姜黄素代谢产物四氢姜黄素抗乳腺癌Hormesis效应的剂量学分析  

Dosage Analysis in the Antitumor Hormesis Effect of Traditional Chinese Medicine Curcumin Metabolite Tetrahydrocurcumin on Breast Cancer

作　　者：孙小虎 王柯乜 曹旭晨 Sun Xiaohu;Wang Kenie;Cao Xuchen(The First Department of Breast Cancer,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer/Ministry of Education Key Laboratory of Breast Cancer Prevention and Therapy,Tianjin Medical University,Tianjin 300060,China)

机构地区：[1]天津医科大学肿瘤医院乳腺肿瘤一科,国家恶性肿瘤临床医学研究中心/肿瘤防治重点实验室/天津市恶性肿瘤临床医学研究中心/乳腺癌防治教育部重点实验室,天津300060

出　　处：《华中科技大学学报(医学版)》2025年第1期8-12,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.82274221)。

摘　　要：目的探究中药姜黄素代谢产物四氢姜黄素(tetrahydrocurcumin,THC)对乳腺癌抗肿瘤Hormesis效应的剂量学分析。方法采用不同浓度的THC对人乳腺癌MCF-7和小鼠乳腺癌4T1细胞系进行处理,通过细胞活力检测、细胞周期检测、测量细胞中的活性氧(reactive oxygen species,ROS)水平、划痕愈合迁移实验以及侵袭实验比较细胞状态。结果与空白对照组相比,小剂量的THC(4、8μmol/L)处理后MCF-7和4T1细胞的增殖活性受到刺激,大剂量THC(16、32μmol/L)处理后MCF-7细胞的增殖活性受到显著抑制。小剂量的THC(2、4、8μmol/L)处理导致MCF-7和4T1细胞的G_(0)/G_(1)期细胞积累减少,S和G_(2)/M期的细胞数量增加。大剂量的THC(16μmol/L和32μmol/L)处理导致MCF-7细胞的G_(0)/G_(1)期细胞积累增加,并且该周期中细胞数量以浓度依赖性方式增加。随着剂量的增加,MCF-7细胞和4T1细胞的ROS水平升高。在低剂量THC(4μmol/L)处理后,MCF-7和4T1细胞的迁移能力和侵袭能力有所增强,而在高剂量(16μmol/L和32μmol/L)时以剂量依赖的方式抑制了MCF-7和4T1细胞的迁移和侵袭能力。结论THC对乳腺癌细胞的影响具有显著的浓度依赖性,低浓度时可能表现出促生长和促转移的特性,而高浓度时则抑制细胞增殖和迁移侵袭,并诱导细胞周期阻滞。Objective To explore the dosimetric influence of tetrahydrocurcumin(THC),a metabolite derived from the Chinese herbal compound curcumin,on the antitumor Hormesis effect observed in breast cancer.Methods Human breast cancer MCF-7 and mouse breast cancer 4T1 cell lines were exposed to THC of various concentrations.Cellular responses were evaluated through a series of assays,including cell viability assessments,cell cycle phase distribution analysis,measurement of intracellular reactive oxygen species(ROS)levels,wound healing migration assays,and invasion assays.Results In comparison to the untreated control group,low concentrations of THC(4,8μmol/L)exhibited a stimulatory effect on the proliferative activity of both MCF-7 and 4T1 cells.Conversely,the proliferative capacity of MCF-7 cells was significantly suppressed under higher concentrations of THC(16,32μmol/L).The accumulation of cells in the G_0/G_(1)phase reduced and the number of cells in the S and G_2/M phases increased for both cell lines under low doses of THC(2,4,8μmol/L).However,G_0/G_(1)phase cells were increased in MCF-7 cells under high doses of THC(16μmol/L and 32μmol/L),and this effect showed a concentration-dependent manner.Additionally,as the THC dose escalated,ROS levels in both MCF-7 and 4T1 cells increased.Following treatment with a low dose of THC(4μmol/L),the migratory and invasive capabilities of both cell lines were enhanced.In contrast,the migration and invasion of both cell lines were inhibited in a dose-dependent manner after high doses THC treatment(16μmol/L and 32μmol/L).Conclusion The effects of THC on breast cancer cells demonstrate a pronounced concentration-dependent pattern.Lower concentrations of THC may exhibit pro-growth and pro-metastatic properties,whereas higher concentrations of THC inhibits cell proliferation,migration,and invasion,and induces cell cycle arrest.

关 键 词：姜黄素 四氢姜黄素 乳腺癌 Hormesis效应 

分 类 号：R737.9[医药卫生—肿瘤]