Modulators of the Nrf2 Signaling Pathway Enhance the Cytotoxic Effect of Standard Chemotherapeutic Drugs on Organoids of Metastatic Colorectal Cancer

被引：0

作者：

Razumovskaya, A. V. ^{[1
,2
]}

Silkina, M. O. ^{[1
,2
]}

Nikulin, S. V. ^{[1
,2
,3
]}

Tonevitsky, A. G. ^{[1
]}

Alekseev, B. Ya. ^{[2
]}

机构：

[1] Higher Sch Econ, Moscow, Russia

[2] Minist Hlth Russian Federat, Natl Med Res Ctr Radiol, Obninsk, Russia

[3] Minist Hlth Russian Federat, Dmitry Rogachev Natl Med Res Ctr Pediat Hematol On, Moscow, Russia

来源：

BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE | 2024年 / 176卷 / 05期

基金：

俄罗斯科学基金会;

关键词：

colorectal cancer; tumor organoids; Nrf2 signaling pathway; brusatol; bardoxolone; DIMETHYL FUMARATE; SENSITIVITY; MODEL;

D O I：

10.1007/s10517-024-06093-0

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The activity of known modulators of the Nrf2 signaling pathway (bardoxolone and brusatol) was studied on cultures of tumor organoids of metastatic colorectal cancer previously obtained from three patients. The effect of modulators was studied both as monotherapy and in combination with standard chemotherapy drugs used to treat colorectal cancer. The Nrf2 inhibitor brusatol and the Nrf2 activator bardoxolone have antitumor activity. Moreover, bardoxolone and brusatol also significantly enhance the effect of the chemotherapy drugs 5-fluorouracil, oxaliplatin, and irinotecan metabolite SN-38. Thus, bardoxolone and brusatol can be considered promising candidates for further preclinical and clinical studies in the treatment of colorectal cancer.

引用

页码：703 / 708

页数：6

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