SERPINE1对结肠癌细胞增殖、迁移、侵袭及凋亡的影响

陈德合; 李登玉; 郭刚; 王杰; 周倩; 李洪涛

doi:10.16016/j.2097-0927.202311079

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SERPINE1对结肠癌细胞增殖、迁移、侵袭及凋亡的影响

基础医学 | 更新时间：2026-01-09

- SERPINE1对结肠癌细胞增殖、迁移、侵袭及凋亡的影响
- Effects of SERPINE1 on proliferation, migration, invasion and apoptosis of colon cancer cells
- 陆军军医大学学报 2024年46卷第15期页码：1751-1762
- 作者机构：
  
  1.750000 银川，宁夏医科大学临床医学院胃肠外科
  2.476000 河南商丘，商丘市第五人民医院普外科
  3.730000 兰州，联勤保障部队第九四〇医院普外科
  4.730000 兰州，甘肃省干细胞与基因药物重点实验室
- 作者简介：
  
  [李洪涛，E-mail: lihongtao528@163.comLI Hongtao, E-mail: lihongtao528@163.com
- 基金信息：
  
  甘肃省自然科学基金(22JR5RA005)
- DOI：10.16016/j.2097-0927.202311079
  中图分类号： R341;R730.23;R735.35
- 收稿：2023-11-16，
  
  修回：2023-12-23，
  
  纸质出版：2024-08-15
- 稿件说明：
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陈德合, 李登玉, 郭刚, 等. SERPINE1对结肠癌细胞增殖、迁移、侵袭及凋亡的影响[J]. 陆军军医大学学报, 2024,46(15):1751-1762.

Dehe CHEN, Dengyu LI, Gang GUO, et al. Effects of SERPINE1 on proliferation, migration, invasion and apoptosis of colon cancer cells[J]. Journal of Army Medical University, 2024, 46(15): 1751-1762.
陈德合, 李登玉, 郭刚, 等. SERPINE1对结肠癌细胞增殖、迁移、侵袭及凋亡的影响[J]. 陆军军医大学学报, 2024,46(15):1751-1762. DOI： 10.16016/j.2097-0927.202311079.

Dehe CHEN, Dengyu LI, Gang GUO, et al. Effects of SERPINE1 on proliferation, migration, invasion and apoptosis of colon cancer cells[J]. Journal of Army Medical University, 2024, 46(15): 1751-1762. DOI： 10.16016/j.2097-0927.202311079.

摘要

目的

探究丝氨酸蛋白酶抑制剂1(serine proteinase inhibitor family E member 1，SERPINE1)在结肠癌中的表达及对结肠癌细胞恶性生物学行为的影响。

方法

通过starBase和TISIDB数据库分析471个结肠癌及41个正常结肠组织中SERPINE1的表达及其与临床分期、预后生存的关系；收集联勤保障部队第九四〇医院5例结肠癌患者癌组织与对应的癌旁组织标本，应用RT-qPCR和Western blot验证SERPINE1在结肠癌中的表达。构建SERPINE1过表达与干扰表达的慢病毒载体，进行结肠癌RKO和LoVo细胞株转染，通过RT-qPCR和Western blot评估SERPINE1过表达和干扰表达的效果，通过细胞计数试剂盒(cell counting kit-8，CCK-8)、克隆形成实验、Transwell实验和Hoechst凋亡细胞核染色评估细胞的增殖、迁移与侵袭能力和细胞的凋亡情况；应用Western blot检测SERPINE1对磷脂酰激酶3(phosphatidyl-inositol 3-kinase，PI3K)/蛋白激酶B(protein kinase B，AKT)信号通路的影响。

结果

数据库分析发现SERPINE1在结肠癌中高表达，且与患者的肿瘤临床分期正相关，与预后总生存期负相关(

0.05)。转染过表达的慢病毒载体后细胞的增殖、迁移与侵袭能力增强，而细胞的凋亡减弱；反之，在转染干扰表达的慢病毒载体后细胞的增殖、迁移与侵袭能力减弱，而细胞的凋亡增强(

0.05)。通过Western blot实验发现转染SERPINE1过表达的慢病毒载体后细胞PI3K和AKT表达无明显变化，而磷酸化PI3K(p-PI3K)和磷酸化AKT(p-AKT)表达增加，反之转染SERPINE1干扰表达的慢病毒载体细胞PI3K和AKT表达无明显变化，而p-PI3K和p-AKT表达减少，灰度值定量分析p-PI3K/PI3K和p-AKT/AKT比值差异有统计学意义(

0.05)。

结论

SERPINE1在结肠癌中高表达，与患者临床分期及预后相关；SERPINE1过表达可能通过激活PI3K/AKT信号通路促进结肠癌细胞的增殖、迁移与侵袭，抑制其凋亡。

Abstract

Objective

To explore the expression of serine proteinase inhibitor family E member 1 (SERPINE1) in colon cancer and its effect on the malignant biological behaviors of colon cancer cells.

Methods

starBase and TISIDB databases were used to analyze the expression of SERPINE1 in 471 patients with colon cancer and 41 paracancerous tissues

and the relationships of its differential expression with clinical stage and prognostic survival were analyzed. The cancer specimens and paracancerous tissues from 5 patients with colon cancer were collected in No. 940 Hospital of Joint Logistic Support Force

and RT-qPCR and Western blotting were employed to detect the expression of SERPINE1 at mRNA and protein levels. After lentiviral vectors of SERPINE1 overexpression and interference were constructed and transfected into colon cancer RKO and LoVo cells. The experimental cells were assessed by RT-qPCR and Western blotting to verify the efficiency of overexpression and interference. Then cell proliferation

migration

invasion and apoptosis were evaluated by CCK-8 assay

clone formation test

Transwell test and Hoechst apoptotic nuclear staining

respectviely. Finally

Western blotting was applied to determine the effect of SERPINE1 on phosphatidyl-inositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.

Results

Database analysis showed that SERPINE1 was highly expressed

positively correlated with the clinical stage and negatively correlated with the overall survival in colon cancer patients (

0.05). Transfection of overexpression lentiviral vector resulted in enhanced cell proliferation

invasion and migration abilities while weakened apoptosis in RKO and LoVo cells. On the contrary

SERPINE1 interference reduced the abilities of cell proliferation

invasion and migration but improved cell apoptosis (

0.05). Western blotting showed that overexpression of SERPINE1 had no effect on the expression of PI3K and AKT

but increased the expression of p-PI3K and p-AKT

and SERPINE1 interference also had no change in PI3K and AKT expression and reduced the levels of their phosphorylation levels. Statistical differences were observed in relative quantitative analysis on the ratios of p-PI3K/PI3K and p-AKT/AKT (

0.05).

Conclusion

SERPINE1 is highly expressed

and correlated with clinical stage and prognosis of patients with colon cancer. Its overexpression promotes the proliferation

migration

invasion and inhibits apoptosis of colon cancer RKO and LoVo cells through PI3K/AKT signaling pathway.

关键词

Keywords

references

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