姜黄素通过下调HIF-1α通路抑制非小细胞肺癌脂质代谢

doi:10.12122/j.issn.1673-4254.2025.05.17

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (5): 1039-1046.doi: 10.12122/j.issn.1673-4254.2025.05.17

• • 上一篇

姜黄素通过下调HIF-1α通路抑制非小细胞肺癌脂质代谢

李丹丹¹^,²(), 楚佳鑫¹^,², 闫妍³, 徐文隽⁴, 朱行春⁴, 孙韵⁴, 丁浩峰⁴, 任丽⁵, 朱博¹^,²()

^1.蚌埠医科大学，基础医学院病理学教研室，安徽蚌埠 233000
^2.蚌埠医科大学，临床医学院，安徽蚌埠 233000
^3.蚌埠医科大学，检验医学院，安徽蚌埠 233000；蚌埠医科大学第一附属医院，安徽蚌埠 233000
^4.蚌埠医科大学，病理科，安徽蚌埠 233000
^5.蚌埠医科大学，麻醉科，安徽蚌埠 233000

收稿日期:2024-08-09 出版日期:2025-05-20 发布日期:2025-05-23
通讯作者: 朱博 E-mail:18756712655@163.com;35736791@qq.com
作者简介:李丹丹，在读硕士研究生，E-mail: 18756712655@163.com
基金资助:
安徽省高校自然科学研究项目(2023AH051998);安徽省高等学校科学研究项目(2022AH051526);蚌埠医科大学研究生科研创新计划项目(Byycx23066)

Curcumin inhibits lipid metabolism in non-small cell lung cancer by downregulating the HIF-1α pathway

Dandan LI¹^,²(), Jiaxin CHU¹^,², Yan YAN³, Wenjun XU⁴, Xingchun ZHU⁴, Yun SUN⁴, Haofeng DING⁴, Li REN⁵, Bo ZHU¹^,²()

^1.Department of Pathology, Bengbu Medical University, Bengbu 233000, China
^2.College of Clinical Medicine, Bengbu Medical University, Bengbu 233000, China
^3.College of Laboratory Medicine, Bengbu Medical University, Bengbu 233000, China
^4.Department of Pathology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China
^5.Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233000, China

Received:2024-08-09 Online:2025-05-20 Published:2025-05-23
Contact: Bo ZHU E-mail:18756712655@163.com;35736791@qq.com

摘要/Abstract

摘要：

目的探讨姜黄素非小细胞肺癌（NSCLC）脂质代谢的作用及其分子机制。方法体外培养A549和H1299细胞，采用MTT法检测姜黄素（0~70 μmol/L）的增殖抑制效应，并筛选20、40 μmol/L用于后续实验。通过细胞摄取实验、伤口愈合实验、甘油三酯（TG）/游离脂肪酸（NEFA）测定及油红O染色评估姜黄素对脂质代谢的影响；Western blotting检测PGC-1α、PPAR-α及HIF-1α表达。网络药理学预测代谢通路，并通过Western blotting验证。体内实验采用裸鼠移植瘤模型，比较姜黄素（20 mg/kg）与对照组的肿瘤质量及脂滴变化。结果姜黄素浓度依赖性抑制NSCLC细胞增殖（P<0.05），并降低TG、NEFA和脂滴含量（P<0.05）。Western blotting显示姜黄素上调PGC-1α和PPAR-α表达（P<0.05）。KEGG通路富集预测发现HIF-1信号通路在姜黄素治疗NSCLC中被显著富集，HIF-1α与PPAR-α之间可能存在相互作用，Western blotting提示姜黄素下调HIF-1α（P<0.05）。动物实验中，姜黄素组肿瘤重量和脂滴减少。结论姜黄素通过HIF-1α通路抑制NSCLC细胞增殖、脂质代谢发生。

关键词: 姜黄素, 非小细胞肺癌, 脂质代谢, HIF-1α通路

Abstract:

Objective To investigate the effect of curcumin on lipid metabolism in non-small cell lung cancer (NSCLC) and its molecular mechanism. Methods The inhibitory effect of curcumin (0-70 μmol/L) on proliferation of A549 and H1299 cells was assessed using MTT assay, and 20 and 40 μmol/L curcumin was used in the subsequent experiments. The effect of curcumin on lipid metabolism was evaluated using cellular uptake assay, wound healing assay, triglyceride (TG)/free fatty acid (NEFA) measurements, and Oil Red O staining. Western blotting was performed to detect the expressions of PGC-1α, PPAR-α, and HIF-1α in curcumin-treated cells. Network pharmacology was used to predict the metabolic pathways, and the results were validated by Western blotting. In a nude mouse model bearing A549 cell xenograft, the effects of curcumin (20 mg/kg) on tumor growth and lipid metabolism were assessed by measuring tumor weight and observing the changes in intracellular lipid droplets. Results Curcumin concentration-dependently inhibited the proliferation of A549 and H1299 cells and significantly reduced TG and NEFA levels and intracellular lipid droplets. Western blotting revealed that curcumin significantly upregulated PGC-1α and PPAR‑α expressions in the cells. KEGG pathway enrichment analysis predicted significant involvement of the HIF-1 signaling pathway in curcumin-treated NSCLC, suggesting a potential interaction between HIF-1α and PPAR‑α. Western blotting confirmed that curcumin downregulated the expression of HIF-1α. In the tumor-bearing mice, curcumin treatment caused significant reduction of the tumor weight and the number of lipid droplets in the tumor cells. Conclusion Curcumin inhibits NSCLC cell proliferation and lipid metabolism by downregulating the HIF-1α pathway.

Key words: curcumin, non-small cell lung cancer, lipid metabolism, HIF-1α pathway

李丹丹, 楚佳鑫, 闫妍, 徐文隽, 朱行春, 孙韵, 丁浩峰, 任丽, 朱博. 姜黄素通过下调HIF-1α通路抑制非小细胞肺癌脂质代谢[J]. 南方医科大学学报, 2025, 45(5): 1039-1046.

Dandan LI, Jiaxin CHU, Yan YAN, Wenjun XU, Xingchun ZHU, Yun SUN, Haofeng DING, Li REN, Bo ZHU. Curcumin inhibits lipid metabolism in non-small cell lung cancer by downregulating the HIF-1α pathway[J]. Journal of Southern Medical University, 2025, 45(5): 1039-1046.

图/表 7

图1 姜黄素对A549和H1299细胞增殖的影响

Fig.1 Inhibitory effect of curcumin on proliferation of A549 and H1299 cells. A, B: Effect of curcumin on viability of A549 and H1299 cells. C, D: Wound healing assay of curcumin-treated A549 and H1299 cells. *P<0.05 vs Curcumin 0; #P<0.05 vs Curcumin 20..

图2 A549和H1299细胞对姜黄素的摄取能力

Fig.2 The ability of A549 and H1299 cells to take up Curcumin.

图3 姜黄素对A549和H1299细胞脂质代谢的影响

Fig.3 Effect of curcumin on lipid metabolism in A549 and H1299 cells. A: Curcumin lowers TG content in A549 and H1299 cells. B: Curcumin lowers NEFA content in A549 and H1299 cells. C: Curcumin reduces lipid drops in A549 and H1299 cells. *P<0.05 vs Curcumin 0; #P<0.05 vs Curcumin 20.

图4 姜黄素对PPAR-α及PGC-1α蛋白表达的影响

Fig.4 Effect of curcumin on PPAR-α and PGC-1α protein expression detected by Western blotting. *P<0.05 vs Curcumin 0; #P<0.05 vs Curcumin 20.

图5 网络药理学分析结果

Fig.5 Results of network pharmacological analysis. A: Venn diagram of NSCLC gene-curcumin target genes. B: PPI network diagram of NSCLC gene-curcumin target genes. C: KEGG enriched pathways for the intersection targets of NSCLC and Curcumin. D: PPI network diagram of adipogenesis.

图6 姜黄素对HIF-1α蛋白表达的影响

Fig.6 Effect of curcumin on HIF-1α protein expression in A549 and H1299 cells. *P<0.05 vs Curcumin 0. #P<0.05 vs Curcumin 20.

图7 姜黄素对裸鼠异种移植瘤的作用

Fig.7 Effect of curcumin on growth of A549 xenografts in nude mice. A, B: Changes in tumor weight in the nude mice. C: Effect of curcumin on lipid droplets in the tumor cells. *P<0.05 vs Control.

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姜黄素通过下调HIF-1α通路抑制非小细胞肺癌脂质代谢

Curcumin inhibits lipid metabolism in non-small cell lung cancer by downregulating the HIF-1α pathway

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