白藜芦醇调控 LncRNA-UCA1/Wnt/β-catenin信号通路抑制非小细胞肺癌的机制研究

Mechanism study of resveratrol regulating LncRNA UCA1/Wnt/β-catenin signaling pathway inhibition of non small cell lung cancer

关键词:  白藜芦醇  LncRNA UCA1  肺癌  Wnt/β-catenin 通路

Key words:  resveratrol  LncRNA UCA1  lung cancer  Wnt/β-catenin pathway

摘要:

[目的] 探讨白藜芦醇通过调控非小细胞肺癌细胞中LncRNA-UCA1的表达，进而影响Wnt/β-catenin信号通路，最后抑制肿瘤细胞的增殖、侵袭并促进凋亡等一系列生物学功能。[方法] 首先探究白藜芦醇对非小细胞肺癌细胞系（A549和Hcc827）的影响，使用细胞活力检测（CCK-8）试剂盒检测细胞活力；Transwell小室和划痕实验验证肿瘤细胞的迁移和侵袭；流式细胞术检测肿瘤细胞的凋亡；Western Blot检测相关通路蛋白（Wnt/β-catenin）的表达情况。随后，应用微阵列技术筛选非小细胞肺癌细胞和正常人肺上皮细胞中异常表达的长链非编码RNA（LncRNA），通过LncRNA-尿路上皮癌抗原1（UCA1）过表达和白藜芦醇共同孵育A549细胞，检测其对肿瘤细胞增殖、迁移、侵袭和凋亡的影响，以及Wnt/β-catenin通路相关蛋白的变化。[结果] 白藜芦醇可以呈剂量依赖性的抑制非小细胞肺癌细胞系（A549和Hcc827）的增殖和侵袭并且促进其凋亡，并且下调Wnt/β-catenin信号通路中的β-catenin、CyclinD1、c-myc蛋白表达；同时，LncRNA-UCA1在非小细胞肺癌细胞系中高表达，而白藜芦醇可显著抑制其表达；此外，过表达LncRNA-UCA1可通过调节Wnt/β-catenin信号通路促进非小肺癌细胞系（A549和Hcc827）的增殖，迁移和侵袭并抑制细胞凋亡，而加入白藜芦醇后可以显著抑制上述效应。[结论] LncRNA-UCA1在非小细胞肺癌细胞系中高表达，而白藜芦醇可以通过下调其表达水平，进而调控Wnt/β-catenin信号通路来抑制非小细胞肺癌细胞的增殖，迁移和侵袭并促进其凋亡。

Abstract:

[Objective] Exploring how resveratrol regulates the expression of LncRNA-UCA1 in non-small cell lung cancer cells，thereby affecting the Wnt/β-catenin signaling pathway，ultimately inhibiting tumor cell proliferation，invasion，and promoting apoptosis，among other biological functions. [Methods] Firstly，investigate the effect of resveratrol on non-small cell lung cancer cell lines（A549 and Hcc827），and detect cell viability using CCK-8 assay kit；Transwell chamber and scratch experiments were conducted to verify the migration and invasion of tumor cells；detection of tumor cell apoptosis by flow cytometry；Western Blot was used to detect the expression of related pathway proteins （Wnt/β-catenin）. Subsequently，microarray technology was applied to screen for LncRNAs with abnormal expression in non-small cell lung cancer cells and normal human lung epithelial cells. A549 cells were co cultured with LncRNA-UCA1 overexpression and resveratrol to detect their effects on tumor cell proliferation，migration，in vasion，and apoptosis，as well as changes inWnt/β-catenin pathway related proteins. [Results] Resveratrol can inhibit the proliferation and invasion of non-small cell lung cancer cell lines（A549 and Hcc827） in a dose-dependent manner，promote their apoptosis，and downregulate the expression of β-catenin，CyclinD1，and c-myc proteins in the Wnt/β-catenin signaling pathway；meanwhile，LncRNA-UCA1 is highly expressed in non-small cell lung cancer cell lines，while resveratrol can significantly inhibit its expression；in addition，overexpression of LncRNA-UCA1 can promote the proliferation，migration，and invasion of non-small lung cancer cell lines（A549 and Hcc827） and inhibit cell apoptosis by regulating the Wnt/β-catenin signaling pathway. The addition of resveratrol can significantly inhibit these effects. [Conclusion] LncRNA-UCA1 is highly expressed in non-small cell lung cancer cell lines，and resveratrol can regulate the Wnt/β-catenin signaling pathway by downregulating its expression level to inhibit the proliferation，migration，and invasion of non-small cell lung cancer cells，and promote their apoptosis.