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Inhibitory Effects of 5-Fluorouracil on the Growth of 4-Hydroxytamoxifen-resistant and Sensitive Breast Cancer Cellsстатья Исследовательская статья
Дата последнего поиска статьи во внешних источниках: 19 июня 2024 г.
- Авторы: Sorokin Danila V., Krymov Stepan K., Cherednichenko Margarita N., Mikhaylova Alexandra L., Salnikova Diana I., Shchekotikhin Andrey E., Scherbakov Alexander M.
- Журнал: Engineering Proceedings
- Том: 5
- Год издания: 2023
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Номер статьи: 16332
- DOI: 10.3390/ASEC2023-16332
- Аннотация: Cancer is one of the leading causes of death worldwide, accounting for about 10 milliondeaths a year, or nearly one in six deaths. The most common types of cancer are breast, colorectal,lung, and prostate cancers. Prolonged application of hormone drugs leads to the development ofresistance. The development of agents with high activity against resistant cells is a challenge. It isimportant to create novel targeted compounds and search for active molecules among previouslydeveloped. The study aimed to evaluate the sensitivity of 4-hydroxytamoxifen-resistant cells to 5-fluorouracil (5-FU) and analyse the signalling pathways that are regulated by 5-FU in breast cancercells. Antiproliferative activity of compounds was assessed by the MTT assay, immunoblotting wasused to evaluate the expression of proteins in breast cancer cells. Activity of 5-FU was evaluated onparental MCF7 cells and a cell subline with resistance to 4-hydroxytamoxifen (HT), namedMCF7/HT. The 4-hydroxytamoxifen-resistant cells showed high sensitivity to 5-FU. Expression ofoestrogen receptor α (a key driver of breast cancer growth) in MCF7 and MCF7/HT cells was notsensitive to 5-FU treatment. In both parental and resistant cells, 5-FU induced changes in the activityof several signalling proteins. 5-FU activated AKT, ERK 1/2 kinases and upregulated cyclin D1 expression. The data suggest that 5-FU should be further investigated as a chemotherapeutic for hormone-resistant cancers; the combination of 5-FU with novel apoptosis inducer LCTA-3344 is considered as effective to inhibit the growth of breast cancer cells, including hormone-resistant.
- Добавил в систему: Сальникова Диана Игоревна