干扰成纤维细胞生长因子-18 对结肠癌细胞的抗肿瘤研究

doi:10.3870/j.issn.1672-8009.2023.04.004

摘要/Abstract

摘要： 目的初步探讨干扰成纤维生长因子 18 (fibroblast growth factor-18, FGF-18) 在结肠癌中的抗肿瘤作用。方法体外培养结肠癌细胞株 SW480, 分为 Control 组、 shRNA-NC 组和 sh-FGF-18 组; 克隆实验检测细胞增殖能力; 流式细胞仪检测细胞凋亡情况; Hoechst 观察凋亡后细胞形态变化; 划痕实验检测细胞迁移能力; Transwell 检测细胞侵袭能力; HE 染色观察小鼠肝和肺组织转移情况; Western 印迹检测上皮间质转化 (epithelial-mesenchymal transition, EMT) 相关标记物 E-钙粘蛋白 (E cadherin, E-cad), N-钙粘蛋白 (N-cadherin, N-cad), 纤维连接蛋白 (fibronectin, FN) 水平; 裸鼠成瘤实验检测肿瘤体积及大小; 免疫组化检测小鼠肿瘤组织 E-cad、 N-cad、 FN 在结肠癌组织中的阳性表达。结果与 shRNA-NC 组比较, FGF-18-shRNA 组细胞 FGF-18 mRNA 和蛋白水平相对表达水平降低, 克隆细胞和侵袭细胞减少, 划痕距离增加, 凋亡细胞增多, E-cad 蛋白水平增加, N-cad 和 FN 蛋白水平减少; E-cad 在 sh-FGF-18 组中的阳性表达高于 shRNA-NC 组, N-cad 和 FN 的表达低于 shRNA-NC 组 (P< 0. 05)。与 shRNA-NC 组比较, sh-FGF-18 组中原发灶瘤体重量变轻, 体积变小 (P< 0. 05), 肝和肺组织表面转移灶较少 (P< 0. 05)。结论干扰 FGF-18 基因表达抑制结肠癌细胞的增殖、迁移和侵袭, 促进凋亡, 抑制裸鼠移植瘤生长能力, 可能通过抑制 EMT 途径影响肿瘤转移。

关键词: 成纤维生长因子 18, 结肠癌, 增殖, 抗肿瘤

Abstract: Objective To explore the effect of fibroblast growth factor 18 (FGF-18) in colon cancer. Methods The colon cancer cell lines (SW480) were cultured in vitro and divided into 3 groups: control group, shRNA-NC group and sh-FGF-18 group. The cells proliferation was detected by colony formation assay. The apoptosis was detected by flow cytometry. The changes of cells morphology after apoptosis were observed by Hoechst. The cell migration was detected by wound healing assay. The cell invasion was detected by Transwell assay. The metastasis of liver and lung tissues was observed by HE staining. The expression levels of epithelial-mesenchymal transition (EMT) related markers [ E-cadherin ( E-cad ), N-cadherin ( N-cad ), fibronectin ( FN)] were detected by Western blotting. The volume and size of tumors were detected by tumor formation assay in nude mice. The positive expressions of E-cad, N-cad and FN in colon cancer tissues were detected by immunohistochemistry. Results Compared with these in the shRNA-NC group, the relative expression levels of FGF-18 mRNA and protein were decreased in the FGF-18-shRNA group, the number of colonies, migrated cells and invasive cells were reduced, the number of apoptotic cells was increased, the expression level of E-cad was increased, and the expression levels of N-cad and FN were decreased. The positive rate of E-cad expression in colon cancer tissues in the sh-FGF-18 group was higher than that in the shRNA-NC group, while the positive rate of N-cad and FN expressions were lower than those in the shRNA-NC group (P< 0. 05). The tumor weight of primary lesions was lower, and the volume was smaller in the sh-FGF-18 group when compared with those in the shRNA-NC group (P< 0. 05), and there were fewer metastases of liver and lung tissues in the sh-FGF 18 group (P< 0. 05). Conclusion Interfering with FGF-18 can inhibit the proliferation, migration and invasion of colon cancer cells, promote apoptosis and inhibit xenograft growth in nude mice, which may affect tumors metastasis by inhibiting EMT pathway.

Key words: fibroblast growth factor 18, colon cancer, proliferation, anti-tumor

中图分类号:

陈希, 张金宁, 姚亚辉, 刘恒. 干扰成纤维细胞生长因子-18 对结肠癌细胞的抗肿瘤研究 [J]. 医学分子生物学杂志, 2023, 20(4): 298-304.

CHEN Xi, ZHANG Jinning, YAO Yahui, LIU Heng. Effect of Fibroblast Growth Factor 18 in Colon Cancer Cells[J]. Journal of Medical Molecular Biology, 2023, 20(4): 298-304.

[1]	廖运国 , 唐梓瑜 , 李超 , 蒲嘉骐 , 邱世香 , 杨甜. LncRNA BLACAT1 调节 miR-324-5p / MAP4K3 轴对肝癌细胞增殖、迁移和侵袭的影响[J]. 医学分子生物学杂志, 2023, 20(4): 324-331.
[2]	梁伟华, 蒋淼. 丙泊酚通过 SFRP1-Wnt 信号通路抑制肠癌细胞增殖侵袭的机制研究[J]. 医学分子生物学杂志, 2023, 20(4): 359-364.
[3]	周金阔, 史晓晶, 刘倩峰, 刘广顺, 姜磊, 张晋弘. miR-27b-3p 靶向 HOXB8 调节口腔鳞癌耐药细胞的增殖、凋亡和顺铂耐药性 [J]. 医学分子生物学杂志, 2023, 20(3): 202-208.
[4]	田莉, 赵济华, 徐晋珩, 胡月明, 崔海军, 曹渤海. LncRNA OSTN-AS1 下调 miR-4461 表达促进前列腺癌 LNCaP 细胞增殖、迁移和侵袭[J]. 医学分子生物学杂志, 2023, 20(3): 215-220.
[5]	吴红琴 , 王曦 , 谭云清 , 杨清 , 张静 , 臧兴双. RABL6 高表达促进口腔鳞癌细胞的增殖、迁移和侵袭[J]. 医学分子生物学杂志, 2023, 20(3): 254-259.
[6]	李新华, 李军, 裴卓, 栾红娟. 翠云草总黄酮通过调控 miR-3662 表达抑制喉鳞癌 TU177 细胞增殖、迁移和侵袭的机制研究[J]. 医学分子生物学杂志, 2023, 20(3): 260-266.
[7]	邓亮亮, 张先梅, 黄婧, 朱彬, 周奇. 敲低 CXCL8 抑制口腔鳞癌的细胞增殖和转移 [J]. 医学分子生物学杂志, 2023, 20(2): 110-116.
[8]	周巧辉, 艾耀伟, 李玲, 颜学良. PTEN-Long 在胃癌细胞中的表达及其过表达对 PI3K/ AKT 信号通路及细胞生长和凋亡的影响[J]. 医学分子生物学杂志, 2023, 20(2): 123-128.
[9]	刘慧 , 王佳 , 张虹丽. PCA3 调控 miR-185 对霍奇金淋巴瘤细胞 L428 增殖和凋亡的影响[J]. 医学分子生物学杂志, 2023, 20(2): 141-147.
[10]	赵伟军, 苗艳凌, 斯日古楞, 李玉石. 蜘蛛香总黄酮调控 miR-4429 影响胃癌 AGS 细胞的增殖、迁移及侵袭[J]. 医学分子生物学杂志, 2023, 20(2): 173-178.
[11]	黄琦, 翟海程. lncRNA CERS6-AS1 通过调控 miR-138-2-3p 抑制人胶质瘤细胞系增殖 [J]. 医学分子生物学杂志, 2023, 20(1): 20-25.
[12]	鲁慧玲, 闫飞艳 , 常丽花. lncRNA PSMA3-AS1 靶向 miR-3619-5p 调控宫颈癌 SiHa 细胞增殖、迁移及侵袭的分子机制研究[J]. 医学分子生物学杂志, 2023, 20(1): 26-33.
[13]	杨永勤 , 路宁 , 张明鑫, . 结肠癌免疫相关 lncRNA 风险预测模型的建立[J]. 医学分子生物学杂志, 2023, 20(1): 34-39.
[14]	郁昊 , 万炳年 , 刘艳萍. CHRDL1 调节结直肠癌增殖、迁移和侵袭[J]. 医学分子生物学杂志, 2023, 20(1): 63-69.
[15]	宋平辉 , 张毅 , 吴忠坤 , 李春博 , 李勤新. HBV HBx 蛋白调控肝癌细胞增殖的机制研究[J]. 医学分子生物学杂志, 2023, 20(1): 70-77.

干扰成纤维细胞生长因子-18 对结肠癌细胞的抗肿瘤研究

Effect of Fibroblast Growth Factor 18 in Colon Cancer Cells

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价