Zeylenone affects colorectal cancer progression by regulating PI3K/AKT-mediated polarization of tumor-associated macrophages
10.3969/j.issn.1000-484X.2024.05.011
- VernacularTitle:山椒子烯酮通过调控PI3K/AKT介导的肿瘤相关巨噬细胞极化影响结直肠癌进展
- Author:
Dengyun LI
1
;
Taoli WANG
;
Lixiao YUE
;
Xinyong ZHAO
;
Shiguang WANG
Author Information
1. 郑州工业应用技术学院医学院,新郑 451100
- Keywords:
Zeylenone;
Colorectal cancer;
PI3K/AKT signaling pathway;
Macrophage
- From:
Chinese Journal of Immunology
2024;40(5):970-976
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the antitumor activity of zeylenone in colorectal cancer and its related regulatory mechanism.Methods:Human colorectal cancer cells(DLD-1 and HCT116)and control cell(HcoEpic)were treated with different concentrations of zeylenone(0,2.5,5,10 and 20 μmol/L)for 48 h.Cell viability of DLD-1,HCT116 and HcoEpic were determined by CCK-8 kit.TUNEL staining was used to evaluate cell apoptosis.Caspase-3 activity and LDH level were measured by ELISA.Relative levels of M1 and M2 polarization markers,p-PI3K/PI3K and p-AKT/AKT were detected by Western blot and qRT-PCR.DLD-1 cells were subcuta-neously injected into the armpit of nude mice to establish a mouse xenograft tumor model.Intraperitoneal dose of zeylenone given to nude mice was 30 mg/kg,administered once every two days.After 2 weeks,the effect of zeylenone on growth of colorectal cancer tumors was detected.Results:Zeylenone inhibited cell activity and promoted cell apoptosis in colorectal cancer cells.Additionally,zeylenone stimulated M1-polarization and inhibited M2-polarization of tumor-associated macrophages(P<0.05).PI3K/AKT signaling pathway was inhibited by zeylenone in colorectal cancer cells(P<0.05).PI3K/AKT signaling pathway activator(740 Y-P)attenuated the effect of zeylenone on colorectal cancer cells.In mouse xenograft model,zeylenone inhibited the growth of colorectal cancer tumors(P<0.05).Conclusion:Zeylenone can inhibit colorectal cancer cell activity,promote colorectal cancer cell apoptosis,and promote M1 po-larization of tumor-associated macrophages by regulating PI3K/AKT signaling pathway,ultimately inhibiting the progression of colorec-tal cancer.
