Adenosine Concentration Determination for in Vitro Tumor Microenvironment Simulation.

IF 2.4 4区医学 Q3 PHARMACOLOGY & PHARMACY

Dose-Response Pub Date : 2025-08-25 eCollection Date: 2025-07-01 DOI:10.1177/15593258251371484

Chun Chen, Chuanpeng Yang, Shuning Hu, Wenjie Nie, Sudan Ye, Minghao Lu, Xingjie Xu, Huajun Hu

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引用次数: 0

Abstract

Objectives: We aimed to investigate the concentration of adenosine (ADO) in the tumor microenvironment (TME), focusing on its potential to modulate tumor cells and natural killer (NK) cells, thereby facilitating tumor immune escape.

Methods: In this study, an in vitro simulation system was developed to systematically evaluate the effects of ADO (0-500 μM) on the colony formation and migration capability of A549 (lung carcinoma) and A375 (melanoma) cell lines, as well as its action on NK92 cell activity, cytokine secretion, and cytotoxicity against tumor cells.

Results: The results showed that 50 μM ADO significantly promoted tumor cell proliferation (increasing the colony formation rate by 60%-80%) and migration (increasing the migration rate by 30%-40%), whereas high concentrations (>200 μM) exhibited an inhibitory effect. ADO suppressed NK92 cell activity in a dose-dependent manner, reducing the relative proliferation rate by 14.5% at 50 μM, significantly decreasing IFN-γ secretion (by 24% at 50 μM), and impairing the killing efficiency of A549, A375, and HepG2 cells (reducing their respective cytotoxicity by 20.3%, 22.4%, and 31.5%).

Conclusion: This study provides biological evidence that 50 μM represents a critical threshold concentration for TME simulation, elucidates the concentration-dependent bidirectional regulation of ADO.

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体外肿瘤微环境模拟中腺苷浓度的测定。

目的：我们旨在研究肿瘤微环境（TME）中腺苷（ADO）的浓度，重点研究其调节肿瘤细胞和自然杀伤细胞（NK）从而促进肿瘤免疫逃逸的潜力。方法：建立体外模拟系统，系统评价ADO （0-500 μM）对A549（肺癌）和A375（黑色素瘤）细胞系集落形成和迁移能力的影响，以及对NK92细胞活性、细胞因子分泌和肿瘤细胞毒性的影响。结果：50 μM的ADO显著促进肿瘤细胞增殖（集落形成率提高60% ~ 80%）和迁移（迁移率提高30% ~ 40%），而高浓度（>200 μM）则表现出抑制作用。ADO以剂量依赖性方式抑制NK92细胞活性，50 μM下相对增殖率降低14.5%，IFN-γ分泌显著降低（50 μM下降低24%），A549、A375和HepG2细胞的杀伤效率降低（分别使其细胞毒性降低20.3%、22.4%和31.5%）。结论：本研究提供了50 μM为TME模拟临界阈值浓度的生物学证据，阐明了ADO的浓度依赖性双向调节。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Dose-Response PHARMACOLOGY & PHARMACY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

CiteScore

4.90

自引率

4.00%

发文量

140

审稿时长

>12 weeks

期刊介绍： Dose-Response is an open access peer-reviewed online journal publishing original findings and commentaries on the occurrence of dose-response relationships across a broad range of disciplines. Particular interest focuses on experimental evidence providing mechanistic understanding of nonlinear dose-response relationships.