肿瘤相关巨噬细胞外泌体调控KRAS信号通路影响胰腺癌细胞糖酵解功能

迪里夏提·阿力木; 郑坚江; 多力坤·吐拉哈孜; 阿木提江·马合木提

doi:10.11659/jjssx.01E023084

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肿瘤相关巨噬细胞外泌体调控KRAS信号通路影响胰腺癌细胞糖酵解功能

基础研究 | 更新时间：2024-04-01

- 肿瘤相关巨噬细胞外泌体调控KRAS信号通路影响胰腺癌细胞糖酵解功能
- Effect of tumor-associated macrophage exosomes on glycolysis of pancreatic cancer cells by regulating KRAS signal pathway
- 局解手术学杂志 2024年33卷第3期页码：208-213
- 作者机构：
  
  新疆维吾尔自治区人民医院肝胆胰医学诊疗中心，新疆乌鲁木齐 830001
- 作者简介：
  
  阿木提江·马合木提，E-mail：540621258@qq.com
- 基金信息：
  
  新疆维吾尔自治区自然科学基金(2018D01C140)
- DOI：10.11659/jjssx.01E023084
  中图分类号： R392.2
- 纸质出版日期：2024-03-25，
  
  收稿日期：2023-11-19，
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迪里夏提·阿力木 ,郑坚江,多力坤·吐拉哈孜等.肿瘤相关巨噬细胞外泌体调控KRAS信号通路影响胰腺癌细胞糖酵解功能[J].局解手术学杂志,2024,33(03):208-213.

Alimu Dilixiati,ZHENG Jian-jiang,Tulahazi Duolikun,et al.Effect of tumor-associated macrophage exosomes on glycolysis of pancreatic cancer cells by regulating KRAS signal pathway[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(03):208-213.
迪里夏提·阿力木 ,郑坚江,多力坤·吐拉哈孜等.肿瘤相关巨噬细胞外泌体调控KRAS信号通路影响胰腺癌细胞糖酵解功能[J].局解手术学杂志,2024,33(03):208-213. DOI： 10.11659/jjssx.01E023084.

Alimu Dilixiati,ZHENG Jian-jiang,Tulahazi Duolikun,et al.Effect of tumor-associated macrophage exosomes on glycolysis of pancreatic cancer cells by regulating KRAS signal pathway[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2024,33(03):208-213. DOI： 10.11659/jjssx.01E023084.

摘要

目的

探究肿瘤相关巨噬细胞外泌体对胰腺癌细胞糖酵解的影响及机制。

方法

THP-1细胞诱导分化为M0型和M2型巨噬细胞，并提取二者分泌的外泌体（M0 exo和M2 exo）。将胰腺癌细胞CAPAN-2和ASPC-1分为PBS组、M0 exo组、M2 exo组、M2 exo+siKRAS组，分别与等体积PBS、10 μg/mL M0 exo、10 μg/mL M2 exo、转染KRAS siRNA+10 μg/mL M2 exo共孵育。透射电镜观察外泌体结构；CCK-8法检测各组细胞增殖能力；试剂盒检测葡萄糖摄取率和乳酸生成水平；Western blot检测外泌体标志物、KRAS蛋白表达和ERK1/2磷酸化水平。

结果

THP-1诱导分化为表达标志蛋白Arg-1和IL-10的M2型巨噬细胞，M0 exo和M2 exo具有双层膜结构，粒径100 nm左右，表达外泌体标志蛋白CD9、CD81、TSG101。与PBS组比较，M2 exo组CAPAN-2和ASPC-1细胞增殖能力、葡萄糖摄取率力、乳酸生成水平显著增加（

0.05），KRAS表达以及ERK1/2磷酸化水平显著增加（

0.001）。与M2 exo组比较，M2 exo+siKRAS组CAPAN-2和ASPC-1细胞增殖能力、葡萄糖摄取率以及乳酸生成水平均显著下降（

0.05）。

结论

肿瘤相关巨噬细胞外泌体可通过激活KRAS信号通路促进胰腺癌细胞糖酵解。

Abstract

Objective

To investigate the effect of tumor-associated macrophage exosomes on glycolysis of pancreatic cancer cells and its mechanism.

Methods

The THP-1 cells were induced to differentiate into the M0 and M2 macrophages， and the exosomes （M0 exo and M2 exo） were extracted. The pancreatic cancer cells CAPAN-2 and ASPC-1 were divided into the PBS group，the M0 exo group，the M2 exo group and the M2 exo+siKRAS group， and co-incubated with equal volumes of PBS， 10 μg/mL of M0 exo， 10 μg/mL of M2 exo， and transfection of KRAS siRNA and 10 μg/mL of M2 exo， respectively. Transmission electron microscopy was used to observe the structure of exosomes； CCK-8 was used to detect the cell proliferation capacity； the kit was used to detect the glucose uptake rate and production level of lactic acid， and Western blot was used to detect the exosome markers expression， KRAS protein expression and ERK1/2 phosphorylation level.

Results

THP-1 was induced to differentiate into M2 macrophages expressing Arg-1 and IL-10 marker proteins. M0 exo and M2 exo had a bilayer membrane structure with a particle size of about 100 nm and expressed exosomal marker proteins of CD9， CD81， and TSG101. Compared with the PBS group， the cell proliferation， glucose uptake rate， production level of lactic acid of CAPAN-2 and ASPC-1 cells in the M2 exo group increased significantly （

0.05）， and the KRAS expression and ERK1/2 phosphorylation level were significantly increased （

0.001）. Compared with the M2 exo group， the proliferation， glucose uptake rate and production level of lactic acid of CAPAN-2 and ASPC-1 cells in the M2 exo+siKRAS group decreased significantly （

0.05）.

Conclusion

Tumor-associated macrophage exosomes can promote the glycolysis of pancreatic cancer cells via the activation of KRAS signaling pathway.

关键词

肿瘤相关巨噬细胞外泌体糖酵解KRAS信号通路

Keywords

tumor-associated macrophagesexosomesglycolysisKRAS signaling pathway

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