| 科罗索酸靶向调节TGF-β1/SMAD2/3通路抑制黑色素瘤增殖和转移 |
| 投稿时间：2024-10-24 修订日期：2024-11-18 点此下载全文 |
| 引用本文：李文娜,王小莉.科罗索酸靶向调节TGF-β1/SMAD2/3通路抑制黑色素瘤增殖和转移[J].医学研究杂志,2025,54(4):116-121 |
| DOI：
10.11969/j.issn.1673-548X.2025.04.021 |
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| 基金项目:陕西省自然科学基础研究计划青年项目(2024JC-YBQN-0946) |
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| 中文摘要:目的 探究科罗索酸对黑色素瘤的治疗作用以及可能的分子机制。方法 培养黑色素瘤B16细胞和A375细胞,均分组为空白组(0μmol/L)、低浓度科罗索酸组(5μmol/L)、中浓度科罗索酸组(10μmol/L)和高浓度科罗索酸组(20μmol/L)。根据分组,使用对应浓度科罗索酸干预培养两种细胞。通过集落形成实验检测细胞增殖活性,划痕实验检测细胞迁移能力,Transwell实验检测细胞侵袭能力。Western blot法检测细胞内转化生长因子-β1(transforming growth factor-β1, TGF-β1)、母亲DPP同源物2(果蝇)[mothers against DPP homolog 2 (Drosophila), SMAD2]、SMAD3、磷酸化SMAD2(p-SMAD2)、磷酸化SMAD3(p-SMAD3)、B淋巴细胞瘤-2(B-cell lymphoma-2, Bcl-2)、Bcl-2-相关X蛋白(Bcl-2-associated X, Bax)和Bcl-2关联死亡启动子(Bcl-2 associated death promoter, Bad)表达水平,细胞免疫荧光实验检测细胞内N-cadherin和Vimentin蛋白表达水平。向上述科罗索酸处理组细胞培养体系内加入TGF-β1重组蛋白进行回复实验。结果 与空白组细胞比较,不同浓度科罗索酸干预均显著抑制了B16细胞和A375细胞的增殖、迁移和侵袭活性,且表现出浓度依赖性。此外,科罗索酸干预导致黑色素瘤细胞内TGF-β1、p-SMAD2、p-SMAD3、Bcl-2、N-cadherin和Vimentin蛋白表达水平显著降低,Bax、Bad蛋白表达水平显著升高,而SMAD2、SMAD3蛋白表达水平无显著变化。加入TGF-β1重组蛋白后,科罗索酸对黑色素瘤细胞的抑制作用得到部分逆转。结论 科罗索酸能够显著抑制黑色素瘤细胞增殖、迁移和侵袭活性,并且与其对TGF-β1/SMAD2/3通路的抑制有关。 |
| 中文关键词:科罗索酸 黑色素瘤 增殖 转移 TGF-β1 SMAD2/3 |
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| Corosolic Acid Targets and Modulates the TGF-β1/SMAD2/3 Pathway to Inhibit Melanoma Proliferation and Metastasis. |
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| Abstract:Objective To explore the therapeutic effect of corosolic acid on melanoma and its possible molecular mechanisms. Methods Melanoma B16 cells and A375 cells were cultured and divided into control group (0μmol/L), low concentration corosolic acid group (5μmol/L), medium concentration corosolic acid group (10μmol/L), and high concentration corosolic acid group (20μmol/L). According to the grouping, the two types of cells were intervened with corresponding concentrations of corosolic acid. Then, the cell proliferation activity was detected by colony formation assay, the cell migration ability was detected by scratch assay, and the cell invasion ability was detected by Transwell assay. Western blot analysis was performed to detect the expression levels of transforming growth factor-β1 (TGF-β1), mothers against DPP hom 2 (Drosophila) (SMAD2), SMAD3, phosphorylated SMAD2 (p-SMAD2), phosphorylated SM3 (p-SMAD3), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), and Bcl-2 associated death promoter (Bad) in cells. Immunofluorescence staining was used to detect the expression levels of N-cadherin and Vimentin in cells. For response experiments, TGF-β1 recombinant protein was added to the cell culture system of the corosamic acid treated groups as described above. Results Compared with the blank group cells, intervention with different concentrations of corosolic acid significantly inhibited the proliferation, migration, and invasion activities of B16 cells and A375 cells, showing a concentration-dependent effect. Additionally, corosolic acid intervention led to a significant decrease in the expression levels of TGF-β1, p-SMAD2, p-SMAD3, Bcl-2, N-cadherin, and Vimentin proteins within melanoma cells, while significantly increasing the expression levels of Bax and Bad proteins. However, there was no significant change in the expression levels of SMAD2 and SMAD3 proteins. After adding recombinant TGF-β1 protein, the inhibitory effect of corosolic acid on melanoma cells was partially reversed.Conclusion Corosolic acid can significantly inhibit the proliferation, migration, and invasion activities of melanoma cells, and this is related to its inhibition of the TGF-β1/SMAD2/3 pathway. |
| keywords:Corosolic acid Melanoma Proliferation Metastasis TGF-β1 SMAD2/3 |
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