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.
Mol Med Rep. 2022 Nov;26(5). doi: 10.3892/mmr.2022.12847. Epub 2022 Sep 7.
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.
肝癌是全球癌症相关死亡的第二大主要原因。本研究旨在评估 M1 样肿瘤相关巨噬细胞（TAMs）的浸润，并探讨 M1 样 TAMs 浸润在肝癌细胞增殖和凋亡逃逸中的作用。此外，还研究了 M1 样 TAM 与肝癌患者术后经导管动脉化疗栓塞（TACE）疗效的关系。通过 Western blot 分析和免疫组织化学检测 CD68、人类白细胞抗原-DR 和磷酸化 NF-κB（p-）p65 的水平。利用细胞周期分析、MTT 和集落形成实验研究肝癌细胞的增殖。结果表明，M1 样 TAM 增加了肝癌细胞中 p-p65/p65 比值，促进了细胞增殖。此外，p65 进入细胞核的抑制剂 JSH-23 降低了 M1 样 TAM 条件培养基中肝癌细胞的增殖。此外，M1 样 TAM 增加了肝癌细胞在细胞周期 S 和 G2/M 期的数量，并上调了周期蛋白依赖性激酶（CDK）1、CDK2 和 cyclin D1 的表达水平。相反，M1 样 TAM 降低了 p21 的表达水平。通过这些作用，增强了肝癌细胞的抗凋亡能力。值得注意的是，JSH-23 逆转了 M1 样 TAM 诱导的肝癌细胞中与细胞周期、抗凋亡能力和蛋白表达相关的这些变化。总之，肝组织中 M1 样 TAM 的浸润对肝癌患者术后 TACE 疗效产生负面影响。
