Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Biological Behavior of HeLa Cells Induced by IL-6 Through STAT3 and AMPK Signaling Pathways
10.13865/j.cnki.cjbmb.2024.07.1050
- VernacularTitle:人脐带间充质干细胞通过STAT3和AMPK信号通路调节白介素-6诱导的HeLa细胞的生物活性
- Author:
Xiao CHEN
1
;
Wan-Ting YAN
;
Lu LIU
Author Information
1. 上海利康瑞生物工程有限公司,上海 201707
- Keywords:
cervical cancer;
interleukin-6;
mesenchymal stem cells(MSCs);
AMP-activated protein kinase(AMPK);
signal transduction transcription activating factor 3(STAT3)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2024;40(9):1262-1272
- CountryChina
- Language:Chinese
-
Abstract:
Cervical cancer is the 4th leading cause of female malignancy-associated mortality worldwide.Surgery and radiotherapy are the main methods of treatment for non-metastatic cervical cancer.There is no clinically effective treatment for the recurrent and metastatic cervical cancer.Therefore,it is particu-larly important to find new and more effective therapeutic targets for cervical cancer treatment.Inflamma-tory response is known to participate in different stages of tumor development.Interleukin-6(IL-6),as a tumor promoting factor,plays a very important role in the development and metastasis of cervical cancer.It has been reported that mesenchymal stem cells play an inhibitory role in a variety of tumors,but there are few reports on their internal mechanism.In addition,the development of cervical cancer is usually accompanied by an increase of IL-6.Whether MSCs can inhibit the proliferation and migration of cervical cancer cells induced by IL-6 in inflammatory conditions is still unknown.This study aimed to explore the effects and mechanism of human umbilical cord mesenchymal stem cells(HUC-MSCs)on the biological activity of HeLa cells induced by IL-6.The colony formation experiment,cell scratch assay and Transwell invasion assay demonstrated that IL-6 significantly promoted HeLa cell proliferation,migration and inva-sion(P＜0.05).Results showed that both 20％and 50％MSCs conditioned medium significantly inhib-ited IL-6-induced proliferation(P＜0.0001),migration(P＜0.01)and invasion(P＜0.0001)of HeLa cells,and IL-6 significantly up-regulated the expression of STAT3 and Bcl-2 genes(P＜0.0001)and protein(P＜0.01)in the anti-apoptosis signaling pathway.At the same time,the expression of AMPK,TSC1 and TSC2 genes was down-regulated(P＜0.001),leading to the up-regulation of metabo-lism related mTOR gene(P＜0.01)and protein(P＜0.05).Furthermore,20％MSCs conditioned medium down-regulated the mRNA and protein expression of STAT3 and Bcl-2(P＜0.05).And 50％MSCs conditioned medium down-regulated the STAT3/Bcl-2 signaling pathway(P＜0.01),up-regula-ted the AMPK/mTOR signaling pathway(P＜0.05)and induced cell cycle arrest(P＜0.0001)signif-icantly in HeLa cells.In summary,MSCs conditioned medium inhibited IL-6-induced HeLa cell prolifer-ation,migration and invasion by down-regulating STAT3 signaling pathway and up-regulating AMPK sig-naling pathway.The results of this study are helpful to further elucidate the role and mechanism of IL-6 in the development of cervical cancer,and provide experimental basis for searching for therapeutic targets of cervical cancer.
