Laboratory of Translation Research, Department of Biomedical Research, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.
Division of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland.
Molecules. 2023 Aug 1;28(15):5808. doi: 10.3390/molecules28155808.
Antimetabolites, especially 5-fluorouracil, are commonly used clinically to treat breast, colon, and other cancers. However, their side effects and inefficiency in monotherapy have prompted further searches for new combinations. Thus, the anticancer effect of 5-fluorouracil (5-FU) and the sulforaphane analogue, 4-isoselenocyanato-1-butyl 4'-fluorobenzyl sulfoxide (ISC), were tested in in vitro and in vivo models of triple-negative breast cancer (TNBC) as a new option for this treatment-resistant and aggressive type of breast cancer. A synergic interaction between 5-FU and ISC was observed in the TNBC in vitro model MDA-MB-231 cell line, which led to enhanced antiproliferative effects. The results of in vitro studies were confirmed by in vivo tests, which demonstrated stronger tumor growth inhibition and additive interactions between 5-FU and ISC in the murine TNBC model. Moreover, the results of the body mass and blood analysis showed the safety of the tested combination. The mechanistic study revealed that the combined treatment triggered apoptosis and necrosis, as well as inhibited cell migration.
抗代谢物，特别是 5-氟尿嘧啶，临床上常用于治疗乳腺癌、结肠癌和其他癌症。然而，它们的副作用和单一疗法的效率低下促使人们进一步寻找新的组合。因此，5-氟尿嘧啶（5-FU）和类硫代葡萄糖苷萝卜硫素类似物 4-异硫氰酸根-1-丁基 4'-氟苄基砜（ISC）的抗癌作用在三阴性乳腺癌（TNBC）的体外和体内模型中进行了测试，作为治疗这种耐药性和侵袭性乳腺癌的新选择。在体外 TNBC 模型 MDA-MB-231 细胞系中观察到 5-FU 和 ISC 之间的协同相互作用，导致增殖抑制作用增强。体外研究的结果得到了体内试验的证实，这些试验表明在小鼠 TNBC 模型中，5-FU 和 ISC 之间的肿瘤生长抑制作用更强，并且存在相加作用。此外，体重和血液分析的结果表明该组合的安全性。机制研究表明，联合治疗触发了细胞凋亡和坏死，并抑制了细胞迁移。
