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拳参提取物通过调控 FAK/PI3K 信号通路抑制胃癌 HGC-27 细胞的分子机制。

The molecular mechanisms of Caulophyllum robustum Maxim extract inhibition by regulating FAK/PI3K signaling pathway in gastric cancer HGC-27 cells.

机构信息

The key laboratory of pathobiology on the tumors with high incidence in Ethics area, State Ethnic Affairs Commission; Cancer Research Center of Yanbian University, Yanji, China.

The key laboratory of pathobiology on the tumors with high incidence in Ethics area, State Ethnic Affairs Commission; Cancer Research Center of Yanbian University, Yanji, China; Chifeng Municipal Hospital, Chifeng, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 2):118867. doi: 10.1016/j.jep.2024.118867. Epub 2024 Oct 5.

DOI:10.1016/j.jep.2024.118867
PMID:39369918
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Caulophyllumrobustum Maxim extract (CRME), as recorded in traditional Chinese medicine, has the function of dispelling Feng, regulating Qi and dredging collaterals, promoting blood circulation and regulating menstruation, gingering up and relieving pain, clearing heat simultaneously detoxifying, lowering blood pressure and hemostasis. CRME is often used as Chinese materia medica preparation for rheumatoid arthritis, traumatic injury, irregular menstruation, abdominal pain, and hypertension treatment. Since gastric cancer (GC) existed as a health problem of human over the years, we are committed to the development of potential components of Chinese herbal medicine curing cancer, and we found CRME is expected to be one of the effective anti-tumor traditional Chinese medicine preparations.

AIMS OF THE STUDY

To investigate the molecular mechanisms of CRME anticancer effects and the potential links between CRME and FAK.

MATERIALS AND METHODS

Caulophyllumrobustum Maxim was extracted to obtain CRME, high-performance liquid chromatography (HPLC) was used for qualitative analysis. Information about CRME was collected from traditional Chinese medicine records and local surveys unpublished internationally. Series of cellular function experiments were applied to detect cell proliferation, migration, apoptosis, autophagy, cell cycle, angiogenesis. The xenograft model is employed in vivo.

RESULTS

CRME can significantly inhibit HGC-27 cells on proliferation, migration and angiogenic capacity. Xenograft model indicated CRME inhibited cell proliferation in vivo. Annexin V-FITC/PI double staining assay and PI single staining assay depicted that CRME induces cell apoptosis, and arrests cell cycle at G0/G1 phase. AO (acridine orange) staining assay showed that CRME promoted autophagosome formation and inhibited autophagic flow. HPLC indicated Cauloside A and Cauloside C are components of CRME. Western blot indicated that FAK/PI3K signaling pathway is critical in the inhibition of CRME on HGC-27 cells.

CONCLUSIONS

The anti-tumor components of CRME, Cauloside A and Cauloside C, inhibited tumor progression in HGC-27 cells. This inhibition is achieved by decreasing the phosphorylation levels of FAK, thereby modulating PI3K/AKT signaling pathway.

摘要

民族药理学相关性

在传统中医中,长春花提取物(CRME)具有祛风、调气、通络、活血调经、行气止痛、清热解毒、降压止血的功能。CRME 常被用作治疗类风湿关节炎、创伤、月经不调、腹痛和高血压的中药制剂。由于胃癌(GC)一直是人类的健康问题,我们致力于开发治疗癌症的中草药潜在成分,我们发现 CRME 有望成为有效的抗肿瘤中药制剂之一。

研究目的

研究 CRME 抗癌作用的分子机制及其与 FAK 的潜在联系。

材料和方法

长春花提取物得到 CRME,高效液相色谱(HPLC)用于定性分析。从传统中药记录和国际上未发表的当地调查中收集有关 CRME 的信息。应用一系列细胞功能实验检测细胞增殖、迁移、凋亡、自噬、细胞周期、血管生成。体内采用异种移植模型。

结果

CRME 能显著抑制 HGC-27 细胞的增殖、迁移和血管生成能力。异种移植模型表明 CRME 抑制了体内细胞的增殖。Annexin V-FITC/PI 双染法和 PI 单染法显示 CRME 诱导细胞凋亡,并将细胞周期阻滞在 G0/G1 期。AO(吖啶橙)染色实验表明,CRME 促进自噬体形成并抑制自噬流。HPLC 表明长春苷 A 和长春苷 C 是 CRME 的成分。Western blot 表明,FAK/PI3K 信号通路在 CRME 抑制 HGC-27 细胞中起关键作用。

结论

CRME 的抗肿瘤成分长春苷 A 和长春苷 C 通过降低 FAK 的磷酸化水平,从而调节 PI3K/AKT 信号通路,抑制 HGC-27 细胞的肿瘤进展。

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