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生长抑素衍生物(smsDX)通过调节核因子κB减轻肿瘤相关巨噬细胞刺激的前列腺癌增殖、迁移和侵袭。

Somatostatin Derivate (smsDX) Attenuates the TAM-Stimulated Proliferation, Migration and Invasion of Prostate Cancer via NF-κB Regulation.

作者信息

Guo Zhaoxin, Xing Zhaoquan, Cheng Xiangyu, Fang Zhiqing, Jiang Chao, Su Jing, Zhou Zunlin, Xu Zhonghua, Holmberg Anders, Nilsson Sten, Liu Zhaoxu

机构信息

Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.

Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

出版信息

PLoS One. 2015 May 26;10(5):e0124292. doi: 10.1371/journal.pone.0124292. eCollection 2015.

Abstract

Tumor development and progression are influenced by macrophages of the surrounding microenvironment. To investigate the influences of an inflammatory tumor microenvironment on the growth and metastasis of prostate cancer, the present study used a co-culture model of prostate cancer (PCa) cells with tumor-associated macrophage (TAM)-conditioned medium (MCM). MCM promoted PCa cell (LNCaP, DU145 and PC-3) growth, and a xenograft model in nude mice consistently demonstrated that MCM could promote tumor growth. MCM also stimulated migration and invasion in vitro. Somatostatin derivate (smsDX) significantly attenuated the TAM-stimulated proliferation, migration and invasion of prostate cancer. Immunohistochemistry revealed that NF-κB was over-expressed in PCa and BPH with chronic inflammatory tissue specimens and was positively correlated with macrophage infiltration. Further investigation into the underlying mechanism revealed that NF-κB played an important role in macrophage infiltration. SmsDX inhibited the paracrine loop between TAM and PCa cells and may represent a potential therapeutic agent for PCa.

摘要

肿瘤的发生和进展受周围微环境中巨噬细胞的影响。为了研究炎性肿瘤微环境对前列腺癌生长和转移的影响,本研究采用前列腺癌细胞与肿瘤相关巨噬细胞(TAM)条件培养基(MCM)的共培养模型。MCM促进前列腺癌细胞(LNCaP、DU145和PC-3)生长,裸鼠异种移植模型也一致表明MCM可促进肿瘤生长。MCM还能在体外刺激细胞迁移和侵袭。生长抑素衍生物(smsDX)显著减弱TAM刺激的前列腺癌增殖、迁移和侵袭。免疫组织化学显示,在前列腺癌和伴有慢性炎性组织标本的良性前列腺增生中,NF-κB过度表达,且与巨噬细胞浸润呈正相关。对潜在机制的进一步研究表明,NF-κB在巨噬细胞浸润中起重要作用。SmsDX抑制TAM与前列腺癌细胞之间的旁分泌循环,可能是一种潜在的前列腺癌治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec6b/4444263/0ce48eeada87/pone.0124292.g001.jpg

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