M1‑like tumor‑associated macrophages enhance proliferation and anti‑apoptotic ability of liver cancer cells via activating the NF‑κB signaling pathway

Sharen,Gaowa; Cheng,Haidong; Hu,Xiuhua; Miao,Jie; Zhao,Defang

doi:10.3892/mmr.2022.12847

M1‑like tumor‑associated macrophages enhance proliferation and anti‑apoptotic ability of liver cancer cells via activating the NF‑κB signaling pathway

Authors:
- Gaowa Sharen
- Haidong Cheng
- Xiuhua Hu
- Jie Miao
- Defang Zhao
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Affiliations: Department of Pathology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010059, P.R. China, Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010059, P.R. China, Department of Hepatobiliary Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010059, P.R. China
Published online on: September 6, 2022 https://doi.org/10.3892/mmr.2022.12847
Article Number: 331
Copyright: © Sharen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is the second leading cause of cancer‑associated death worldwide. The present study aimed to evaluate the infiltration of M1‑like tumor‑associated macrophages (TAMs) and explore the role of infiltration of M1‑like TAMs in the proliferation and apoptosis evasion of liver cancer cells. Furthermore, the association between M1‑like TAM and the efficacy of postoperative transcatheter arterial chemoembolization (TACE) for patients with liver cancer was investigated. The levels of CD68, human leukocyte antigen‑DR and phosphorylated NF‑κB (p‑)p65 were detected by western blot analysis and immunohistochemistry. Cell cycle analysis, MTT and clonogenic assays were utilized to investigate the proliferation of liver cancer cells. It was indicated that M1‑like TAM increased the p‑p65/p65 ratio in liver cancer cells and promoted cell proliferation. Furthermore, JSH‑23, an inhibitor that prevents p65 from entering the nucleus, decreased the proliferation of liver cancer cells in M1‑like TAM‑conditioned medium. In addition, M1‑like TAM increased the number of liver cancer cells in the S and G2/M phases of the cell cycle and also upregulated the expression levels of cyclin‑dependent kinase (CDK)1, CDK2 and cyclin D1. By contrast, M1‑like TAM decreased the expression level of p21. Through these effects, the anti‑apoptotic ability of liver cancer cells was enhanced. Of note, JSH‑23 reversed these changes related to the cell cycle, anti‑apoptotic ability and the expression levels of proteins induced by M1‑like TAM in liver cancer cells. In conclusion, the infiltration of M1‑like TAM in liver tissue negatively influenced the efficacy of postoperative TACE for patients with liver cancer.

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