Home Neoplasma 2022 Neoplasma Vol.69, No.2, p.331–340, 2022

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Neoplasma Vol.69, No.2, p.331–340, 2022

Title: Liver X receptors agonist T0901317 exerts ferroptosis sensitization in cancer
Author: Meng-Ting Zhou, Zhen-Yu Li, Jun Fan, Pin-Dong Li, Ye Wang, Sheng Zhang, Xiao-Fang Dai

Abstract: Numerous studies have confirmed the anticancer effects of ferroptosis on a wide range of tumors, specifically in providing new perspectives for tackling drug resistance and treating refractory tumors. Notably, mechanisms of improving tumor susceptibility to ferroptosis have been a focus of current research. This study discovered that co-treatment of LXRS agonist T0901317 and ferroptosis inducers (FINs) significantly inhibited the proliferation of cancer cells, this inhibition effect could be reversed by specific inhibitors of ferroptosis and accompanied by elevated lipid peroxides. Glutathione peroxidase 4 (GPX4) regulates T0901317 induced ferroptotic sensitization, and its overexpression dramatically reverses the joint anticancer effect of T0901317 and FINs. Furthermore, xenograft model results highly confirmed the ferroptotic sensitization effect of T0901317 in vivo. In summary, our findings indicate that drug combination and ferroptosis induction strategies provide novel options for cancer therapy.

Keywords: liver X receptors; ferroptosis; agonist; sensitivity; drug combination
Published online: 27-Jan-2022
Year: 2022, Volume: 69, Issue: 2 Page From: 331, Page To: 340
doi:10.4149/neo_2021_210810N1132


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