The potential anti-cancer properties of selenium (Se) and eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) have been documented. However, few studies have been conducted examining anti-tumor effects of nutritional supplements (NS) containing Se and EPA/DHA in combination with anti-cancer agents, such as taxol (Tax), adriamycin (Adr), and avastin (Ava). Compared with triple-negative breast cancer (TNBC)-bearing positive control (TB) mice, a low dose of Tax, Adr, and Ava decreased tumor size and the incidence of metastasis in TB-Tax, TB-Adr, and TB-Ava groups. Combination treatment with anti-cancer agent and NS (2.7 μg Se and 5.1 mg EPA/3.7 mg DHA/g) induced additional decreases in TB-Tax-NS, TB-Adr-NS, and TB-Ava-NS groups. Th1-associated cytokines were increased, and Th2-type cytokines were decreased significantly in TB mice with combination treatment than that of anti-cancer agent treatment alone. Combination treatment with anti-cancer agents and NS has also been shown to further increased tumor malondialdehyde (MDA) levels, lowered hypoxia-inducible factor (HIF)-1α, angiogenic markers (vascular endothelial growth factor [VEGF] and CD31) and metastatic potential, as well as reduced heat shock proteins, receptor tyrosine kinase AXL, and surface markers of cancer stem cells, and increased apoptotic proteins. For immune checkpoint molecules, combination treatment was associated with a greater decrease in programmed cell death ligand-1 (PD-L1) in both tumors and mammary glands, but PD-1 level in primary tumors was increased. Our results suggest that combination treatment with low-dose anti-cancer agents (Tax, Adr, and Ava) and oral supplementation of Se/ EPA/DHA significantly decreased tumor growth and metastatic progression in TNBC mice through multiple anti-tumor mechanisms.

硒 (Se) 和二十碳五烯酸 (EPA)/二十二碳六烯酸 (DHA) 的潜在抗癌特性已被记录在案。然而，很少有研究检测含有 Se 和 EPA/DHA 的营养补充剂 (NS) 与抗癌剂，如紫杉醇 (Tax)、阿霉素 (Adr) 和阿瓦斯汀 (Ava) 的组合的抗肿瘤作用。与携带三阴性乳腺癌 (TNBC) 的阳性对照 (TB) 小鼠相比，低剂量的 Tax、Adr 和 Ava 降低了 TB-Tax、TB-Adr 和 TB-Ava 的肿瘤大小和转移发生率组。用抗癌剂和 NS（2.7 μg Se 和 5.1 mg EPA/3.7 mg DHA/g）联合治疗会导致 TB-Tax-NS、TB-Adr-NS 和 TB-Ava-NS 组的额外减少。Th1 相关细胞因子增加，与抗癌药物单独治疗相比，联合治疗的TB小鼠体内的Th2型细胞因子和Th2型细胞因子显着降低。抗癌药物和 NS 联合治疗也显示出进一步增加肿瘤丙二醛 (MDA) 水平，降低缺氧诱导因子 (HIF)-1α、血管生成标志物（血管内皮生长因子 [VEGF] 和 CD31）和转移潜能，以及减少热休克蛋白、受体酪氨酸激酶 AXL 和癌症干细胞的表面标志物，并增加凋亡蛋白。对于免疫检查点分子，联合治疗与肿瘤和乳腺中程序性细胞死亡配体-1 (PD-L1) 的更大减少有关，但原发肿瘤中的 PD-1 水平增加。我们的结果表明，与低剂量抗癌药物（Tax、