Tumor-associated macrophages (TAM) are key regulators of the link between inflammation and cancer, and the interplay between TAM and tumor cells represents a promising target of future therapeutic approaches. We investigated the effect of gallic acid (GA) and caffeic acid (CA) as strong antioxidant and anti-inflammatory agents on tumor growth, angiogenesis, macrophage polarization, and oxidative stress on the angiogenic model caused by the intraperitoneal (ip) inoculation of Ehrlich ascites tumor (EAT) cells (2.5 × 106) in Swiss albino mouse. Treatment with GA or CA at a dose of 40 mg/kg and 80 mg/kg ip was started in exponential tumor growth phase on days 5, 7, 9, and 11. On day 13, the ascites volume and the total number and differential count of the cells present in the peritoneal cavity, the functional activity of macrophages, and the antioxidant and anti-angiogenic parameters were determined. The results show that phenolic acids inhibit the processes of angiogenesis and tumor growth, leading to the increased survival of EAT-bearing mice, through the protection of the tumoricidal efficacy of M1 macrophages and inhibition of proangiogenic factors, particularly VEGF, metalloproteinases -2 and -9, and cyclooxygenase-2 activity.

中文翻译：

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天然酚酸，蜜蜂的产物，用于控制小鼠的氧化应激、腹膜血管生成和肿瘤生长

肿瘤相关巨噬细胞 (TAM) 是炎症和癌症之间联系的关键调节剂，TAM 与肿瘤细胞之间的相互作用代表了未来治疗方法的一个有希望的目标。我们研究了没食子酸 (GA) 和咖啡酸 (CA) 作为强抗氧化剂和抗炎剂对肿瘤生长、血管生成、巨噬细胞极化和由 Ehrlich 腹腔 (ip) 接种引起的血管生成模型的氧化应激的影响瑞士白化小鼠腹水肿瘤 (EAT) 细胞 (2.5 × 106)。在第 5、7、9 和 11 天的指数肿瘤生长期开始以 40 mg/kg 和 80 mg/kg 剂量的 GA 或 CA ip 治疗。 在第 13 天，腹水体积和总数和差异存在于腹腔中的细胞计数，巨噬细胞的功能活动，并测定抗氧化和抗血管生成参数。结果表明，酚酸通过保护 M1 巨噬细胞的杀瘤功效和抑制促血管生成因子，特别是 VEGF、金属蛋白酶 -2 和 - 来抑制血管生成和肿瘤生长过程，从而提高携带 EAT 的小鼠的存活率。 9、环氧合酶-2活性。