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Title: | In vitro exosomal transfer of Nrf2 led to the oxaliplatin resistance in human colorectal cancer LS174T cells | Authors: | Mostafazadeh, Mostafa KAHROBA, Houman Haiaty, Sanya TazeKand, Abbas P. Samadi, Nasser Rahbarghazi, Reza Nouri, Mohammad |
Issue Date: | 2022 | Publisher: | WILEY | Source: | CELL BIOCHEMISTRY AND FUNCTION, | Status: | Early view | Abstract: | Chemotherapy resistance is a serious pitfall in the treatment of colon cancers (CCs). Previous studies have found that exosomes (Exo) play a pivotal role in tumor drug resistance via the transfer of proteins and genetic materials to the acceptor cells. To date, the mechanisms orchestrating Exo-derived resistance in cancer cells have been the center of attention. Herein, we aimed to evaluate the role of exosomal nuclear factor erythroid 2-related factor 2 (Nrf2) on oxaliplatin (1-OHP) resistance in human colorectal cancer LS174T cells in vitro. To this end, exosomal-Nrf2-mediated 1-OHP resistance was examined using different assays. Exo was isolated from resistant LS174T cells (LS174T/R) and added to the culture medium of sensitive LS174T cells (LS174T/S). According to our data, LS174T/S cells successfully adsorbed PKH26-Exo driven from LS174T/R cells. Western blotting showed an increased Nrf2 level in Exo isolated from LS174T/R cells compared to LS174T/S cell-derived Exo (p < .05). The incubation of LS174T/S cells with LS174T/R-derived Exo increased half-maximal inhibitory concentration values in response to treatment with 1-OHP (p < .05). Besides this, the apoptotic changes were diminished in LS174T/S cells after incubation with LS174T/R-derived Exo. Of note, the exposure of LS174T/S cells to LS174T/R cell-derived Exo increased the expression of Nrf2 and P-glycoprotein (P-gp) compared to the nontreated LS174T/S cells (p < .05). In line with these changes, lower intracellular Rhodamin 123 content was detected in Exo-treated cells compared to the nontreated LS174T/S cells. Exo increased migration and clonogenic capacity of LS174T/S cells after incubation with Exo-derived from resistant cells. Of note, inhibition of Nrf2 with a specific blocker, brusatol, blunted these effects. Taken together, Exo-mediated transfer of Nrf2 is involved in the development of oxaliplatin resistance in CC cells by upregulating P-gp. | Notes: | Rahbarghazi, R; Nouri, M (corresponding author), Tabriz Univ Med Sci, Stem Cell Res Ctr, Imam Reza St,Golgasht St, Tabriz 5166614756, Iran. Rezarahbardvm@gmail.com; Nourimd@yahoo.com |
Keywords: | chemoresistance;exosomes;human colorectal cancer LS174T cells;Nrf2;oxaliplatin | Document URI: | http://hdl.handle.net/1942/37398 | ISSN: | 0263-6484 | e-ISSN: | 1099-0844 | DOI: | 10.1002/cbf.3703 | ISI #: | WOS:000787732100001 | Rights: | 2022 John Wiley & Sons Ltd. | | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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In vitro exosomal transfer of Nrf2 led to the oxaliplatin resistance in human colorectal cancer LS174T cells.pdf Restricted Access | Published version | 3.55 MB | Adobe PDF | View/Open Request a copy |
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