College of Food Science and Nutritional Engineering, China Agricultural University, Haidian District, No.17 Qinghua East Road, Beijing, 100083, China.
College of Veterinary Medicine, China Agricultural University, Haidian District, No.2 Yunamingyuan West Road, Beijing, 100193, China.
Biol Trace Elem Res. 2024 Aug;202(8):3565-3573. doi: 10.1007/s12011-023-03927-2. Epub 2023 Oct 28.
Drug combination is considered to be an effective approach to improve the efficacy of cancer therapy and chemoprevention. Selenite, a representative of inorganic form of selenium, and butyrate, a major short-chain fatty acid, are two well-documented colon cancer dietary chemopreventive agents with distinct molecular mechanisms. We hypothesized that combination of selenite and butyrate might produce improved outcome against colon cancer. This hypothesis was tested using both HCT116 human colon cancer cells and its xenograft mouse model in the present study. The in vitro study showed a synergistically inhibitory effect on HCT116 colon cancer cells but not on NCM460 normal human colon mucosal epithelial cells. Consistent with the in vitro study, results of the xenograft mouse model further demonstrated that combination of selenite and butyrate led to improved efficacy in comparison with each agent alone. Mechanistically, the induction of alanine-serine-cysteine transporter 2 (ASCT2) by selenite repressed its inhibitory effect on colon cancer cells, which was reversed by its co-treatment with butyrate. The findings of the present study denote the likely potential for developing selenite/butyrate combination remedy to combat against colon cancer.
联合用药被认为是提高癌症治疗和化学预防效果的有效方法。亚硒酸盐是一种具有代表性的无机硒形式，丁酸盐是一种主要的短链脂肪酸，它们都是具有明确分子机制的结肠癌饮食化学预防剂。我们假设亚硒酸盐和丁酸盐的联合使用可能会改善结肠癌的治疗效果。本研究采用 HCT116 人结肠癌细胞及其异种移植小鼠模型对这一假说进行了验证。体外研究表明，该联合用药对 HCT116 结肠癌细胞具有协同抑制作用，但对 NCM460 正常人类结肠黏膜上皮细胞没有这种作用。与体外研究一致，异种移植小鼠模型的结果进一步表明，与单独使用每种药物相比，亚硒酸盐和丁酸盐的联合使用可提高疗效。从机制上讲，亚硒酸盐诱导丙氨酸-丝氨酸-半胱氨酸转运蛋白 2（ASCT2）的表达，从而抑制了其对结肠癌细胞的抑制作用，而丁酸盐的共同处理则逆转了这一作用。本研究的结果表明，开发亚硒酸盐/丁酸盐联合疗法来对抗结肠癌具有很大的潜力。
