The Potential Role of Nrf2-PD-L1 Axis in Promoting of Oxaliplatin Resistance in Colon Cancer Cells

Payandeh, Zahra; Tazehkand, Abbas Pirpour; Mansoori, Behzad; Khaze, Vahid; Asadi, Milad; Samadi, Nasser; Baradaran, Behzad

doi:10.21203/rs.3.rs-58926/v1

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References 59 publications

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“…These features confirm the critical role of Nrf2 in the control of resistance in cancer cells in response to chemotherapeutic agents. In line with our results, Payandeh et al 29,30 previously showed that the suppression of Nrf2 using small interfering RNA can reduce the resistance of CC cells to 1‐OHP. So far, several mechanisms have been proposed for the promotion of resistance to anticancer agents.…”

Section: Discussionsupporting

confidence: 92%

“…These features confirm the critical role of Nrf2 in the control of resistance in cancer cells in response to chemotherapeutic agents. In line with our results, Payandeh et al 29,30 33 In another study, Exo harboring ubiquitin carboxy-terminal hydrolase-L1-mediated adriamycin resistance in breast cancer cells. 34 Concerning drug resistance in CC, several different proteins have been identified.…”

Section: Discussionsupporting

confidence: 91%

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In vitro exosomal transfer of Nrf2 led to the oxaliplatin resistance in human colorectal cancer LS174T cells

Mostafazadeh

Kahroba

Haiaty

et al. 2022

Cell Biochemistry & Function

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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.

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Section: Discussionsupporting

confidence: 92%

“…These features confirm the critical role of Nrf2 in the control of resistance in cancer cells in response to chemotherapeutic agents. In line with our results, Payandeh et al 29,30 33 In another study, Exo harboring ubiquitin carboxy-terminal hydrolase-L1-mediated adriamycin resistance in breast cancer cells. 34 Concerning drug resistance in CC, several different proteins have been identified.…”

Section: Discussionsupporting

confidence: 91%