Programme Stricto Sensu in Health Science, Sao Francisco University Medical School, Sao Paulo, Brazil.
These authors contributed equally to this work.
Oncotarget. 2022 Feb 8;13:307-318. doi: 10.18632/oncotarget.28181. eCollection 2022.
Tumor cells trigger angiogenesis through the expression of angiogenic factors. Vasohibins (VASHs) are a family of peptides that regulate angiogenesis. Flavonoids have antiproliferative antitumor properties; however, few studies have highlighted their antiangiogenic potential. This study evaluated the flavonoid isoquercetin (Q3G) as an antitumor compound related to colon cancer vascularization and regulation of VASH1 and 2. Mice bearing xenogeneic colon cancer ( = 15) were divided into 3 groups: Q3G-treated (gavage, daily over a week), bevacizumab-treated (intraperitoneal, single dose), or untreated animals. Tumor growth, histological characteristics, blood vessel volume, and VASH1 and 2 expressions were analyzed. Q3G impaired tumor growth and vascularization, upregulated VASH1, and downregulated VASH2 in comparison to untreated animals. Mice treated with Q3G showed approximately 65% fewer blood vessels than untreated animals and 50% fewer blood vessels than mice treated with bevacizumab. Thus, we show that Q3G has antitumor activity, impairs vascularization, and differentially modulates VASH1 and 2 expressions in colon cancer.
肿瘤细胞通过表达血管生成因子来触发血管生成。血管抑制素(VASHs)是一类调节血管生成的肽。类黄酮具有抗增殖抗肿瘤特性;然而,很少有研究强调其抗血管生成潜力。本研究评估了黄酮异槲皮苷(Q3G)作为一种与结肠癌血管生成和 VASH1 和 2 调节相关的抗肿瘤化合物。携带异种结肠癌的小鼠(= 15)分为 3 组:Q3G 治疗组(灌胃,每周一次,连续一周)、贝伐单抗治疗组(腹腔内,单次剂量)或未治疗动物组。分析肿瘤生长、组织学特征、血管体积以及 VASH1 和 2 的表达。与未治疗动物相比,Q3G 可抑制肿瘤生长和血管生成,上调 VASH1 并下调 VASH2。与未治疗动物相比,接受 Q3G 治疗的小鼠的血管数量减少了约 65%,与接受贝伐单抗治疗的小鼠相比,血管数量减少了 50%。因此,我们表明 Q3G 具有抗肿瘤活性,可破坏血管生成,并在结肠癌中差异调节 VASH1 和 2 的表达。