Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases & the Department of Oncology of the First Affiliated Hospital, Hainan Medical University, Haikou 570102, PR China.
Key Laboratory of Natural Products Research and Development from Li Folk Medicine of Hainan Province, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571199, PR China.
Biomed Pharmacother. 2024 Aug;177:117013. doi: 10.1016/j.biopha.2024.117013. Epub 2024 Jun 19.
Dendrobin A, a typical active ingredient of the traditional Chinese medicine Dendrobium nobile, has potential clinical application in cancer treatment; however, its effect and mechanism in anti-hepatocellular carcinoma (HCC) remain unsolved.
The effects of Dendrobin A on the viability, migration, invasion, cycle, apoptosis, and epithelial-mesenchymal transition of HepG2 and SK-HEP-1 cells were verified by in vitro experiments. mRNA sequencing was performed to screen the differentially expressed genes (DEGs) of HCC cells before and after Dendrobin A treatment, following GO enrichment and KEGG signaling pathway analyses. Mechanistically, molecular docking was used to evaluate the binding of Dendrobin A with proteins p65 and p50, before further verifying the activation of nuclear factor kappa-B (NF-κB) signaling. Finally, the antiproliferative effect of Dendrobin A on HCC cells was explored through animal experiments.
Dendrobin A arrested cell cycle, induced apoptosis, and inhibited proliferation, migration, invasion, and blocked epithelial-mesenchymal transition in HepG2 and SK-HEP-1 cells. mRNA sequencing identified 830 DEGs, involving various biological processes. KEGG analysis highlighted NF-κB signaling. Molecular docking revealed strong binding of Dendrobin A with p65 and p50 proteins, and western blotting confirmed reduced levels of p-p65 and p-p50 in HCC cells post Dendrobin A treatment. NF-κB agonist PMA reversed Dendrobin A-inhibited cell proliferation migration and invasion. In vivo experiments showed that Dendrobin A inhibited HCC cell growth.
Our findings suggest that Dendrobin A exhibits anti-HCC properties by inhibiting the activation of the NF-κB pathway. These results provide a scientific basis for utilizing Dendrobium nobile in anti-HCC therapies.
作为传统中药铁皮石斛的典型活性成分，冬凌草甲素在癌症治疗方面具有潜在的临床应用价值；然而，其在抗肝癌（HCC）中的作用和机制仍未得到解决。
通过体外实验验证了冬凌草甲素对 HepG2 和 SK-HEP-1 细胞活力、迁移、侵袭、周期、凋亡和上皮-间充质转化的影响。对冬凌草甲素处理前后 HCC 细胞的差异表达基因（DEGs）进行 mRNA 测序，进行 GO 富集和 KEGG 信号通路分析。通过分子对接评估冬凌草甲素与 p65 和 p50 蛋白的结合情况，进一步验证核因子 kappa-B（NF-κB）信号的激活情况。最后，通过动物实验探索冬凌草甲素对 HCC 细胞的增殖抑制作用。
冬凌草甲素阻滞细胞周期，诱导细胞凋亡，抑制 HepG2 和 SK-HEP-1 细胞增殖、迁移、侵袭和阻断上皮-间充质转化。mRNA 测序鉴定出 830 个 DEGs，涉及多种生物学过程。KEGG 分析突出了 NF-κB 信号。分子对接显示冬凌草甲素与 p65 和 p50 蛋白具有强结合性，Western blot 证实 HCC 细胞中 p-p65 和 p-p50 水平降低。NF-κB 激动剂 PMA 逆转了冬凌草甲素抑制 HCC 细胞增殖、迁移和侵袭的作用。体内实验表明，冬凌草甲素抑制 HCC 细胞生长。
本研究表明，冬凌草甲素通过抑制 NF-κB 通路的激活表现出抗 HCC 特性。这些结果为利用铁皮石斛进行抗 HCC 治疗提供了科学依据。
