肿瘤微环境中的巨噬细胞可能在前列腺癌细胞的进展和转移中发挥调节作用。然而，巨噬细胞与前列腺癌细胞之间的相互作用还不清楚。本研究阐明了炎性巨噬细胞在体外调节人类前列腺癌细胞增殖和死亡的机制。利用Transwell室将RAW264.7小鼠巨噬细胞与PC-3或DU-145野生型细胞体外共培养。RAW264.7细胞在存在脂多糖（LPS）的情况下与PC-3或DU-145细胞共培养。这种共培养阻止了癌细胞的增殖并加速了死亡。有趣的是，从用LPS处理过的RAW264.7细胞获得的条件培养基的添加可抑制癌细胞的增殖并促进其死亡。与LPS培养的细胞相比，RAW264.7细胞在培养基中增加了肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的产生。条件培养基对PC-3或DU-145细胞增殖和死亡的影响可被NF-κB或STAT3信号抑制剂阻断。此外，州内钙蛋白超表达的癌细胞中不表达条件培养基对前列腺癌细胞增殖和死亡的影响，该蛋白可减少NF-κB p65和STAT3的水平。培养细胞与细胞外TNF-α、IL-6或州内钙蛋白可抑制PC-3野生型细胞的增殖。TNF-α或IL-6刺激提高了PC-3细胞中州内钙蛋白的水平。本研究证明，炎性巨噬细胞通过NF-κB、STAT3或州内钙蛋白的信号传导过程促使前列腺癌细胞失去。版权所有©2023 Elsevier Inc. 发表。

Macrophages in the cancer microenvironments may play a regulatory role in the progression and metastasis of prostate cancer cells. However, the crosstalk between macrophages and prostate cancer cells is poorly understood. This study elucidates whether inflammatory macrophages regulate the proliferation and death of human prostate cancer cells in vitro. The RAW264.7 mouse macrophages were cocultured with PC-3 or DU-145 wild-type cells by using a Transwell chamber in vitro. RAW264.7 cells were cocultured with PC-3 or DU-145 cells in the presence of lipopolysaccharide (LPS). This coculturing blocked the proliferation and accelerated the death of cancer cells. Interestingly, cancer cell proliferation was repressed and death was promoted by the addition of the conditioned medium obtained from RAW264.7 cells treated with LPS. Culturing with LPS mostly augmented the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the culture medium of RAW264.7 cells. The effects of the conditioned medium on the proliferation and death of PC-3 or DU-145 cells were blocked by NF-κB or STAT3 signaling inhibitors. Moreover, the effects of the conditioned medium on the proliferation and death of prostate cancer cells were not expressed in regucalcin-overexpressing cancer cells that diminish the levels of NF-κB p65 and STAT3. Culturing with extracellular TNF-α, IL-6, or regucalcin triggered inhibition of the proliferation of PC-3 wild-type cells. The levels of regucalcin in PC-3 cells were elevated by TNF-α or IL-6 stimulation. This study demonstrates that inflammatory macrophages triggered the loss of prostate cancer cells via the signaling process of NF-κB, STAT3, or regucalcin.Copyright © 2023. Published by Elsevier Inc.