摘要: |
目的 分析结直肠腺瘤、结直肠癌组织及肠癌细胞中早幼粒细胞白血病蛋白(promyelocytic leukemia protein,PML)的表达情况,探讨PML在结直肠癌发生发展中的作用。方法 采用免疫组化、Western印迹法检测PML在结直肠癌、结直肠腺瘤及正常结直肠组织中的表达情况。检测10种不同肠癌细胞株的PML表达情况,筛选合适的细胞株进行细胞迁移、侵袭实验。建立PML沉默、过表达肠癌细胞模型,进行细胞迁移、侵袭、增殖、凋亡实验。并分析PML表达对血管表皮生长因子(vascular endothelial growth factor,VEGF)、表皮生长因子受体(epidermal growth factor receptor,EGFR)表达的影响。结果 与正常组织相比,PML在腺瘤组织中表达下降,在肠癌组织中表达进一步下降(P<0.05)。在10种不同的肠癌细胞株中,PML表达较低的细胞侵袭力较强。沉默PML后,肠癌细胞的迁移、侵袭、增殖率升高,凋亡率下降(P<0.05);而PML高表达的肠癌细胞则迁移、侵袭、增殖率下降,凋亡增高(P<0.05)。沉默PML后,肠癌细胞EGFR、VEGF的表达均增加;而PML高表达的肠癌细胞EGFR、VEGF表达均下降(P<0.05)。结论 PML在腺瘤组织中呈低表达,在肠癌组织中表达进一步降低;过表达则可抑制肠癌细胞的迁移、侵袭、增殖,促进凋亡,其机制可能与其对VEGF、EGFR的负调控有关。 |
关键词: 结直肠腺瘤 结直肠癌 早幼粒细胞白血病蛋白 侵袭力 |
DOI:10.12025/j.issn.1008-6358.2022.20211765 |
分类号:R735.3 |
基金项目:国家自然科学基金(82000623,81800478),江苏省自然科学基金(BK20181082),上海市科委重点专项(20DZ1100102),厦门市医疗卫生指导项目(3502Z20209060,3502Z20199178),复旦大学附属中山医院创新基金(2020ZSCX06),复旦大学附属中山医院厦门医院孵化项目(2018ZSXMNK03,2019ZSXMYS06). |
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The role of promyelocytic leukemia protein in the carcinogenesis of colorectal adenoma |
CHEN Bai-sheng1, LI Ping2, ZHOU Ying1, WU Xing-yu1, CHEN Wei-feng2, ZHOU Ping-hong2, GONG Yao-yao3, LIN Sheng-li2
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1.Endoscopy Center, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen 361000, Fujian, China;2.Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China;3.Department of Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China
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Abstract: |
Objective To analyze expression of promyelocytic leukemia protein (PML) in colorectal adenoma, colorectal cancer tissues, and colorectal cancer cells, and to explore the role of PML in the occurrence and development of colorectal cancer. Methods The expression level of PML in colorectal cancer, colorectal adenoma, and normal colorectal mucosa were detected by immunohistochemistry and Western blotting. The expression of PML in 10 different colorectal cancer cell lines were detected, and suitable cell lines were screened for further cell migration, and invasion tests. Furthermore, PML silenced and overexpressed colorectal cancer cell models were established, and cell migration, invasion, proliferation, and apoptosis experiments were performed. The effects of PML on vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expressions were analyzed. Results Compared with normal tissue, the expression of PML decreased in adenoma tissue and further decreased in colorectal cancer tissue (P<0.05). Among the 10 different colorectal cancer cell lines, the cells with lower PML expression were more invasive. After silencing PML, the migration, invasion, and proliferation rates of colorectal cancer cells increased, and apoptosis decreased (P<0.05); while the migration, invasion, and proliferation rates of colorectal cancer cells decreased with high expression of PML, and apoptosis increased (P<0.05). After silencing PML, the expressions of EGFR and VEGF in colorectal cancer cells were significantly increased (P<0.05); while the expressions of EGFR and VEGF in colorectal cancer cells decreased significantly with high PML expression (P<0.05). Conclusion PML is lowly expressed in colorectal adenoma tissue, and its expression is further reduced in colorectal cancer tissue. PML can inhibit the migration, invasion, and proliferation of colorectal cancer cells, and promote their apoptosis, through the negative regulation of VEGF and EGFR. |
Key words: colorectal adenoma colorectal cancer promyelocytic leukemia protein invasiveness |