AMPK/CCL18 Axis Regulates the M2 Transformation of TAMs,Promoting Proliferation,Migration and Invasion of Cervical Cancer Cells
10.3969/j.issn.1671-7414.2025.03.009
- VernacularTitle:AMPK/CCL18轴调控TAMs的M2型转化促进宫颈癌细胞增殖、迁移和侵袭的实验研究
- Author:
Zuchun WANG
1
;
Liehong WANG
1
;
Qingling QI
1
Author Information
1. 青海红十字医院妇科,西宁 810000
- Publication Type:Journal Article
- Keywords:
cervical cancer;
tumor microenvironment;
tumor-associated macrophages;
malignant biological behavior;
AMP-activated protein kinase;
chemokine CC ligand 18
- From:
Journal of Modern Laboratory Medicine
2025;40(3):47-51,58
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate how tumor-associated macrophages(TAMs)in cervical cancer cells respond to AMPK through phenotypic transformation.Methods RT-qPCR and Western blot were used to detect AMPK expression in cervical cancer tissues and HeLa,SiHa and Caski cell lines.The AMPK knockout cell line of HeLa cells was generated using the siRNA technique.The malignant biological behavior of cancer cells mediated by the AMPK/CCL18 axis was investigated using CCK-8,scratch assay and Transwell assay.Cell conditioned medium from each group was collected,and cervical cancer cell conditioned medium was co-cultured with human mononuclear cells(THP-1)to assess THP-1 recruitment and the expression of macrophage typing related markers.The impact of AMPK on tumor proliferation was also evaluated in nude mice.Results QRT-PCR and Western blot analysis showed that the mRNA(1.78±0.30)and protein(1.71±0.33)expression levels of AMPK in cancer tissues were significantly higher than those in adjacent tissues(1.00±0.10,1.00±0.11),and the differences were statistically significant(t=5.966,4.990,all P<0.01).Compared with normal cervical epithelial cells(HUCEC),the mRNA and protein expression of AMPK were significantly increased in three cell lines(HeLa,SiHa,Caski),and the differences were statistically significant(F=5.958,3.457,all P<0.01).Compared with the NC group,knocking down AMPK inhibited the proliferation of cervical cancer cells(1.33±0.18 vs 0.82±0.25),migration(180.07±7.64 vs 126.98±29.00),and invasion(115.90±13.19 vs 68.61±12.87)in cervical cancer cells,with statistical significance(t=4.015,4.337,6.285,all P<0.01).The study found that THP-1 cells exhibited significant reductions in migration(49.34±3.91 vs 33.96±10.94),invasion(28.54±3.06 vs 19.54±6.16)and M2-type polarization(1.01±0.13 vs 0.55±0.11)when AMPK reduction was induced,and these differences were statistically significant(t=3.242,3.207,6.510,all P<0.01).In vivo experiments further supported these findings,showing that AMPK reduction led to significant decreases in tumor volume(721.56±93.70mm3 vs 520.02±47.54mm3)and weight(1.19±0.06g vs 0.86±0.20g),with statistically significant differences(t=4.289,3.582,P<0.01).Conclusion Through modulating M2 polarization in TAMs,the AMPK/CCL18 axis increases cervical cancer cells'proliferation,migration and invasion.AMPK/CCL18 inhibition could provide novel therapeutic targets and approaches for cervical cancer treatment.
