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Chemotherapeutic Agents Sensitize Resistant Cancer Cells to the DR5-Specific Variant DR5-B more Efficiently than to TRAIL by Modulating the Surface Expression of Death and Decoy Receptorsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 29 июля 2020 г.
- Авторы: Аrtykov Аrtem А., Belov Dmitry A., Shipunova Victoria O., Trushina Daria B., Deyev Sergey M., Dolgikh Dmitry A., Kirpichnikov Mikhail P., Gasparian Marine E.
- Журнал: Cancers
- Том: 12
- Номер: 5
- Год издания: 2020
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Первая страница: 1129
- Последняя страница: 1129
- DOI: 10.3390/cancers12051129
- Аннотация: TRAIL is considered a promising antitumor agent because it causes apoptosis of transformed cells without affecting normal cells. However, many types of tumors are cytokine resistant, and combination therapy with various chemotherapeutic drugs is being developed to overcome the resistance. We have demonstrated that the combination of TRAIL with doxorubicin, bortezomib, and panobinostat dramatically reduced the viability of TRAIL-resistant A549 and HT-29 cells. Chemotherapy even more efficiently sensitized cells to the DR5-specific mutant variant of TRAIL DR5-B, which does not have an affinity for decoy receptors. Bortezomib and doxorubicin greatly enhanced the surface expression of the death receptors DR5 and DR4, while panobinostat increased expression of DR5 and suppressed expression of DR4 in both cell lines. All drugs increased surface expression of the decoy receptors DcR1 and DcR2. Unlike the combined treatment, if the cells were pretreated with chemotherapy for 24 h, the cytotoxic activity of TRAIL was less pronounced, while sequential treatment of cells enhanced the effectiveness of DR5-B. The same results were obtained with agonistic anti-DR5 antibodies. Thus, the effectiveness of TRAIL was rather limited due to changes in the ratio of death and decoy receptors and DR5-specific agonists may be preferred in combination antitumor therapy regimens.
- Добавил в систему: Артыков Артем Александрович