Curcumol inhibits hepatocellular carcinoma proliferation through miRNA-124/STAT3 pathway: Network pharmacology and experimental validation

IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Current Research in Biotechnology Pub Date : 2025-01-01 DOI:10.1016/j.crbiot.2024.100270

Gui-yu Li , Ji-yong Lin

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Abstract

Objective

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is one of the most common global cancers. Curcuma zedoaria (Christm.) Roscoe is a traditional Chinese herb that has been used for thousands of years in China to treat various types of cancer. Curcumol is one of its primary bioactive sesquiterpenes and has been reported to possess antitumor properties; however, the underlying mechanisms in hepatocellular carcinoma (HCC) are largely unknown. The aim of this study was to reveal the mechanism of curcumol treating HCC based on the network pharmacology and experimental verification.

Materials and Methods

Targets of HCC and curcumol were identified. The drugs and disease targets were intersected by Venn Diagram. The KEGG pathway enrichment analysis of curcumol treating HCC was analyzed through the R 3.6.1 software. The effects of curcumol on the inhibition of HCC cell line HepG2 growth and its pro-apoptotic activity were evaluated by cell counting kit-8 and flow cytometry. The expression of microRNA-124 (miRNA-124) mRNA was detected by quantitative real-time PCR. HepG2 cells were transfected with a miRNA mimic and inhibitor. The expression of STAT3 and its phosphorylation were induced by IL-6 and detected by western blotting.

Results

MicroRNAs in cancer is a significant enrichment signaling pathway for curcumol treating HCC, according to the KEGG pathway analysis. Curcumol effectively inhibited HepG2 cell growth at 50–150 μg/ml, while it had low toxicity to normal LO2 cells. Using flow cytometry, curcumol strongly promoted apoptosis in HepG2 cells and was more potent than the miRNA-124 mimic, whereas the miRNA-124 inhibitor reduced the pro-apoptotic effect of curcumol. Western blotting revealed that curcumol significantly downregulated the overexpression of STAT3 and its phosphorylation in interleukin-6 induced HepG2 cells, whereas an increased level of STAT3 was observed in the miRNA-124 inhibitor transfected cells after curcumol treatment compared to untransfected cells. The level of miRNA-124 was changed up to 5.87-fold by curcumol treatment.

Conclusions

The mechanism underlying the effect of curcumol on inhibition and pro-apoptosis of HepG2 cell growth is possibly related to the miRNA-124/STAT3 pathway.

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莪术醇通过miRNA-124/STAT3通路抑制肝癌细胞增殖：网络药理学及实验验证

目的肝细胞癌（HCC）是最常见的肝癌类型，也是全球最常见的癌症之一。莪术（圣诞节）罗斯科是一种传统的中国草药，在中国已经使用了数千年，用于治疗各种类型的癌症。姜黄酚是其主要生物活性倍半萜之一，据报道具有抗肿瘤特性；然而，肝细胞癌（HCC）的潜在机制在很大程度上是未知的。本研究旨在通过网络药理学和实验验证，揭示姜黄酚治疗肝癌的机制。材料与方法确定肝癌和姜黄酚的治疗靶点。通过维恩图将药物与疾病靶点相交。通过r3.6.1软件分析姜黄酚治疗HCC的KEGG通路富集分析。采用细胞计数试剂盒-8和流式细胞术观察莪术酚对肝癌细胞株HepG2生长的抑制作用及其促凋亡活性。采用实时荧光定量PCR检测microRNA-124 (miRNA-124) mRNA的表达。用miRNA模拟物和抑制剂转染HepG2细胞。IL-6诱导STAT3表达及磷酸化，western blotting检测。结果根据KEGG通路分析，肿瘤中的microrna是姜黄酚治疗HCC的重要富集信号通路。莪术酚在50 ~ 150 μg/ml浓度下能有效抑制HepG2细胞的生长，对正常LO2细胞的毒性较低。流式细胞术发现，姜黄酚能显著促进HepG2细胞凋亡，且比miRNA-124模拟物更有效，而miRNA-124抑制剂则降低了姜黄酚的促凋亡作用。Western blotting结果显示，姜黄酚显著下调白细胞介素-6诱导的HepG2细胞中STAT3的过表达及其磷酸化，而与未转染的细胞相比，姜黄酚处理后转染miRNA-124抑制剂的细胞中STAT3的水平升高。经姜黄酚处理后，miRNA-124的表达水平变化达5.87倍。结论姜黄酚抑制HepG2细胞生长和促凋亡的机制可能与miRNA-124/STAT3通路有关。

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来源期刊

Current Research in Biotechnology Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

6.70

自引率

3.60%

发文量

审稿时长

38 days

期刊介绍： Current Research in Biotechnology (CRBIOT) is a new primary research, gold open access journal from Elsevier. CRBIOT publishes original papers, reviews, and short communications (including viewpoints and perspectives) resulting from research in biotechnology and biotech-associated disciplines. Current Research in Biotechnology is a peer-reviewed gold open access (OA) journal and upon acceptance all articles are permanently and freely available. It is a companion to the highly regarded review journal Current Opinion in Biotechnology (2018 CiteScore 8.450) and is part of the Current Opinion and Research (CO+RE) suite of journals. All CO+RE journals leverage the Current Opinion legacy-of editorial excellence, high-impact, and global reach-to ensure they are a widely read resource that is integral to scientists' workflow.