Role of Dual Oxygenase 2 (DUOX2) in preventing PD-L1 upregulation and increasing radiosensitivity of stomach cancer cells
AuthorMartins, Mariana B.
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AbstractHuman Stomach cancer cells (NCI-N87) expressing endogenous or downregulated DUOX2 levels were injected into the abdomen of nude mice which were then treated with five 15cGy fractions of Low Dose WART (LD-WART) for three consecutive days. Our data indicate that expression of DUOX2 increased the levels of protein oxidation in mice serum exposed to LD-WART and increased the odds of preventing cancer dissemination by ten-fold. Moreover, downregulation of DUOX2 leads to HIF-1 and PD-L1 up-regulation in human tumors grown in mice. We also observed the same correlation in mice stomach cancer cells (NCC-S192) when DUOX2 was knockdown by CRISPR/Cas9. The upregulation of HIF-1 indicates that these tumors are hypoxic, which contributes to radioresistance. In addition, PD-L1, a downstream target of HIF-1, is also associated with radio-resistance. A mouse angiogenesis profiler array indicated that several angiogenetic factors were upregulated in the DUOX2 positive but not negative tumors in response to LDWART. This could have contributed to increase reoxygenation in the DUOX2 positive tumor and increase radiosensitivity to low dose radiation. The role of LD-WART in the immune response was then investigated in immunocompetent C57BL/6 mice. The mice were exposed to the same regimen of 15cGy LD-WART twice a day for three consecutive days either once or for two consecutive weeks. Samples were then collected one, two, or three weeks later following the last radiation dose. Our data indicate that LD-WART significantly increased CD8+ T cells (Lag3-/PD1-) in the blood and spleen one week following LD-WART and gradually faded off. On the other hand, exposing the mice to two consecutive rounds of LDWRT fail to upregulate the CD8+ T cells.
DescriptionPoster presented at the 12th Annual Cancer Biology Research Retreat, June 9, 2022
Rights/TermsAttribution-NonCommercial-NoDerivatives 4.0 International
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/19136
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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International