Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China; Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, Australia.
Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, Australia; Department of Biosciences, Sardar Patel University, Vallabhvidyanagar, Gujarat, India.
Biomed Pharmacother. 2018 Oct;106:247-254. doi: 10.1016/j.biopha.2018.06.126. Epub 2018 Jun 28.
Disparate roles exist for tumor-associated macrophages in breast cancer growth and progression. The aim of this study was to explore the influence of induced macrophages on the growth of breast cancer cells. THP-1 monocytes were differentiated to macrophages using phorbol 12-myristate 13-acetate. The effect of the medium from THP-1 monocytes or macrophage-conditioned medium (MφCM) on MCF-7 (estrogen receptor and progesterone-positive positive) and MDA-MB-231 (MB; triple-negative) breast cancer cells was determined at 24 h, 48 h and 72 h. Assays were conducted for cell viability, apoptosis, proliferation and cell phenotype, and quantitative real-time polymerase chain reaction (qRT-PCR) for expression of associated genes. MφCM inhibited proliferation of MCF-7 and MB cells in a time-dependent manner and, in particular, decreased viability of MCF-7 cells. MφCM induced a markedly vacuolated phenotype in MCF-7 increased apoptosis in MCF-7 cells, but correlative changes in Bcl-2 or Bax were absent. A multifold and significant reduction in anti-apoptotic Bcl-2 in MB cells was not matched by increased apoptosis. The cell cycle inhibitor CDKN1A was increased in both cell lines, but PCNA decreased only in MB cells. Senescence-associated galactosidase beta-1 (GLB1) mRNA was decreased in MCF-7 cells (48 and 72 h) but increased in MB cells (72 h). Increased expression of interleukin-6 (IL-6) and IL-8 was seen in both cell lines, and increased tumor necrosis factor- α was seen at 24 h for MB and 72 h for MCF-7 indicating increased inflammatory responses of the cancer cells. The two breast cancer celllines had different responses to MφCM, mainly involving inhibition rather than stimulation of growth of the cells, stimulation of senescence (MB cells) and increased inflammatory cytokine expression. The estrogen and progesterone receptor status of the cell lines may determine their response to MφCM. The function of the inflammatory cytokines in breast cancer growth remains to be identified.
肿瘤相关巨噬细胞在乳腺癌的生长和进展中发挥着不同的作用。本研究旨在探讨诱导巨噬细胞对乳腺癌细胞生长的影响。使用佛波醇 12-肉豆蔻酸 13-乙酸酯将 THP-1 单核细胞分化为巨噬细胞。在 24、48 和 72 小时时，测定来自 THP-1 单核细胞或巨噬细胞条件培养基（MφCM）对 MCF-7（雌激素受体和孕激素阳性）和 MDA-MB-231（MB；三阴性）乳腺癌细胞的影响。进行细胞活力、细胞凋亡、增殖和细胞表型测定，以及相关基因的定量实时聚合酶链反应（qRT-PCR）。MφCM 以时间依赖性方式抑制 MCF-7 和 MB 细胞的增殖，特别是降低 MCF-7 细胞的活力。MφCM 在 MCF-7 中诱导明显的空泡化表型，增加 MCF-7 细胞的凋亡，但 Bcl-2 或 Bax 没有相关性变化。MB 细胞中抗凋亡 Bcl-2 的倍数和显著减少并没有被凋亡增加所匹配。两种细胞系中的细胞周期抑制剂 CDKN1A 均增加，但仅在 MB 细胞中 PCNA 减少。衰老相关β-半乳糖苷酶 1（GLB1）mRNA 在 MCF-7 细胞中减少（48 和 72 小时），但在 MB 细胞中增加（72 小时）。两种细胞系均可见白细胞介素-6（IL-6）和 IL-8 的表达增加，而肿瘤坏死因子-α仅在 MB 细胞中 24 小时和 MCF-7 细胞中 72 小时增加，表明癌细胞的炎症反应增加。两种乳腺癌细胞系对 MφCM 的反应不同，主要涉及对细胞生长的抑制而不是刺激、衰老的刺激（MB 细胞）和促炎细胞因子表达的增加。细胞系中雌激素和孕激素受体的状态可能决定其对 MφCM 的反应。炎性细胞因子在乳腺癌生长中的作用仍有待确定。
