Department of Nutrition, Institute of Biomedical Nutrition, Hung-Kuang University, Taichung 433, Taiwan.
Taiwan Nutraceutical Association, Taipei 104, Taiwan.
Mar Drugs. 2021 May 4;19(5):262. doi: 10.3390/md19050262.
Despite the effectiveness of primary treatment modalities for cancer, the side effects of treatments, medication resistance, and the deterioration of cachexia after disease progression lead to poor prognosis. A supportive treatment modality to overcome these limitations would be considered a major breakthrough. Here, we used two different target drugs to demonstrate whether a nutraceutical formula (fish oil, Se yeast, and micronutrient-enriched nutrition; NuF) can interfere with cancer cachexia and improve drug efficacy. After Lewis lung cancer (LLC) tumor injection, the C57BL/6 mice were orally administered targeted therapy drugs Iressa and Sutent alone or combined with NuF for 27 days. Sutent administration effectively inhibited tumor size but increased the number of lung metastases in the long term. Sutent combined with NuF had no significant difference in tumor weight and metastasis compare with Sutent alone. However, NuF slightly attenuated metastases number in lung may via mesenchymal marker N-cadherin suppression. NuF otherwise increased epithelial-like marker E-cadherin expression and induce NO-mediated intrinsic apoptotic pathway in tumor cells, thereby strengthening the ability of the targeted therapy drug Iressa for inhibiting tumor progression. Our results demonstrate that NuF can promote the anticancer effect of lung cancer to targeted therapy, especially in Iressa, by inhibiting HIF-1α and epithelial-mesenchymal transition (EMT) and inducing the apoptosis of lung cancer cells. Furthermore, NuF attenuates cancer-related cachectic symptoms by inhibiting systemic oxidative stress.
尽管癌症的主要治疗方法有效，但治疗的副作用、药物耐药性以及疾病进展后恶病质的恶化导致预后不良。克服这些限制的支持性治疗方法将被视为重大突破。在这里，我们使用两种不同的靶向药物来证明营养配方（鱼油、酵母硒和富含微量营养素的营养；NuF）是否可以干扰癌症恶病质并提高药物疗效。在 Lewis 肺癌（LLC）肿瘤注射后，C57BL/6 小鼠经口给予靶向治疗药物易瑞沙和苏特恩单独或联合 NuF 治疗 27 天。苏特恩的给药有效地抑制了肿瘤大小，但在长期内增加了肺转移的数量。苏特恩联合 NuF 与单独使用苏特恩相比，在肿瘤重量和转移方面没有显著差异。然而，NuF 略微减轻了肺转移的数量，可能是通过抑制间充质标志物 N-钙粘蛋白。NuF 还通过诱导肿瘤细胞中 NO 介导的内在凋亡途径，增加上皮样标志物 E-钙粘蛋白的表达，从而增强靶向治疗药物易瑞沙抑制肿瘤进展的能力。我们的结果表明，NuF 通过抑制 HIF-1α 和上皮-间充质转化（EMT）并诱导肺癌细胞凋亡，可促进肺癌对靶向治疗的抗癌作用，特别是对易瑞沙的作用。此外，NuF 通过抑制全身氧化应激来减轻与癌症相关的恶病质症状。
