姜黄素及其代谢产物四氢姜黄素对乳腺癌MCF-7/ADR细胞多柔比星耐药的逆转作用及其可能的机制OA
Curcumin and its metabolite tetrahydrocurcumin reverse doxorubicin resistance in MCF-7/ADR breast cancer cells:possible mechanisms
目的:探讨姜黄素及其代谢产物四氢姜黄素对乳腺癌多柔比星耐药细胞MCF-7/ADR耐药性的逆转作用及其可能机制.方法:采用CCK-8法检测姜黄素和四氢姜黄素对MCF-7/ADR细胞增殖的抑制作用及对多柔比星耐药性的逆转作用;采用划痕愈合实验和Transwell实验分别检测细胞迁移和侵袭能力;采用流式细胞术检测细胞凋亡;采用实时荧光定量PCR和WB法分别检测谷胱甘肽S-转移酶π-1(GSTP1)、Janus激酶1(JAK1)和信号转导与转录激活因子3(STAT3)mRNA,以及GSTP1、JAK1、磷酸化JAK1(p-JAK1)、STAT3 和磷酸化 STAT3(p-STAT3)蛋白的表达.结果:姜黄素和四氢姜黄素均呈浓度依赖性抑制MCF-7/ADR细胞增殖,四氢姜黄素的IC50为(18.62±2.15)μmol/L,显著低于姜黄素的(37.45±3.28)μmol/L(P<0.05);两者均可增强多柔比星对MCF-7/ADR细胞增殖的抑制作用,四氢姜黄素的耐药逆转指数(4.82)高于姜黄素(2.96)(P<0.05).两种药物均呈浓度依赖性抑制MCF-7/ADR细 胞 迁 移和侵袭并促进细胞凋 亡,同时下调GSTP1、JAK1和STAT3 mRNA,以及GSTP1、p-JAK1和p-STAT3蛋白的表达(与0 μmol/L组相比,均P<0.05).与0 μmol/L组相比,80 μmol/L姜黄素或四氢姜黄素处理后,细胞划痕愈合率和侵袭细胞数均显著降低,细胞凋亡率显著升高(均P<0.05).结论:姜黄素及其代谢产物 四 氢 姜 黄 素 可逆转乳腺癌MCF-7/ADR细胞对多柔比星的耐药性,其机制可能与抑制细胞迁移和侵袭、促进细胞凋亡、下调GSTP1表达,以及抑制JAK1和STAT3的磷酸化有关.
Objective:To investigate the effects of curcumin and its metabolite tetrahydrocurcumin on reversing doxorubicin resistance in MCF-7/ADR breast cancer cells and to explore the possible mechanisms.Methods:The inhibitory effects of curcumin and tetrahydrocurcumin on MCF-7/ADR cell proliferation and their effects on the reversal of doxorubicin resistance were assessed using the CCK-8 assay.Cell migration and invasion were evaluated using wound-healing and Transwell assays,respectively.Apoptosis was analyzed by flow cytometry.The mRNA levels of glutathione S-transferase pi 1(GSTP1),Janus kinase 1(JAK1),and signal transducer and activator of transcription 3(STAT3),as well as the protein levels of GSTP1,JAK1,phosphorylated JAK1(p-JAK1),STAT3,and phosphorylated STAT3(p-STAT3),were measured by quantitative real-time PCR and WB assay,respectively.Results:Both curcumin and tetrahydrocurcumin inhibited MCF-7/ADR cell proliferation in a concentration-dependent manner.The IC₅₀ of tetrahydrocurcumin(18.62±2.15)μmol/L was significantly lower than that of curcumin(37.45±3.28)μmol/L(P<0.05).Both compounds enhanced the inhibitory effect of doxorubicin on MCF-7/ADR cell proliferation,and the resistance reversal index of tetrahydrocurcumin(4.82)was significantly higher than that of curcumin(2.96)(P<0.05).Compared with the 0 μmol/L groups,both compounds inhibited MCF-7/ADR cell migration and invasion in a concentration-dependent manner,promoted apoptosis,and downregulated GSTP1,JAK1,and STAT3 mRNA expression as well as GSTP1,p-JAK1,and p-STAT3 protein expression(all P<0.05).Treatment with 80 μmol/L curcumin or tetrahydrocurcumin significantly reduced the wound-healing rate and the number of invading cells and significantly increased the apoptosis rate(all P<0.05).Conclusion:Curcumin and its metabolite tetrahydrocurcumin can reverse doxorubicin resistance in MCF-7/ADR breast cancer cells,possibly by inhibiting cell migration and invasion,promoting apoptosis,downregulating GSTP1 expression,and suppressing the phosphorylation of JAK1 and STAT3.
孙小虎;王蕴华;刘燕;孟然;曹旭晨
天津医科大学肿瘤医院 国家恶性肿瘤临床医学研究中心,天津 300060||天津市肿瘤防治重点实验室,天津 300060||天津市恶性肿瘤临床医学研究中心,天津 300060||乳腺癌防治教育部重点实验室,天津 300060天津中医药大学 公共卫生与健康科学学院,天津 300193天津市中医药研究院附属医院 药学部,天津 300091天津医科大学肿瘤医院 国家恶性肿瘤临床医学研究中心,天津 300060||天津市肿瘤防治重点实验室,天津 300060||天津市恶性肿瘤临床医学研究中心,天津 300060||乳腺癌防治教育部重点实验室,天津 300060天津医科大学肿瘤医院 国家恶性肿瘤临床医学研究中心,天津 300060||天津市肿瘤防治重点实验室,天津 300060||天津市恶性肿瘤临床医学研究中心,天津 300060||乳腺癌防治教育部重点实验室,天津 300060
医药卫生
谷胱甘肽S-转移酶π-1JAK1/STAT3信号通路姜黄素四氢姜黄素乳腺癌耐药性多柔比星
glutathione S-transferase pi 1(GSTP1)JAK1/STAT3 signaling pathwaycurcumintetrahydrocurcuminbreast cancerdrug resistancedoxorubicin
《中国肿瘤生物治疗杂志》 2026 (7)
746-753,8
国家自然科学基金(82274221)天津市医学重点学科(专科)建设项目(TJYXZDXK-009A)
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