Role of mTOR signaling pathway in regulating CD4 + Treg glucose metabolism in ovarian cancer
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R737.31

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    Abstract:

    Objective:To explore the role of mTOR signaling pathway in CD4 + regulatory T cell(Treg)glucose metabolism in ovarian cancer patients. Methods:Flow cytometry was used to detect the percentage of mTOR+ CD4 + Treg in peripheral blood with ovarian cancer(OC)patients,benign ovarian tumor(BOT)patients and healthy controls(HC). We established a coculture system of human CD4+ Treg with ovarian cancer cell SKOV3,and detected the percentage of mTOR+ CD4+ Treg before and after co-culture. After mTOR signal was inhibited by rapamycin,the glucose uptake and glycolysis levels of CD4+ Treg were detected by colorimetry,and the expression levels of genes and proteins related to glucose metabolism in CD4 + Treg were detected by real-time quantitative PCR and Western blot. Results:The percentage of mTOR+ CD4+ Treg in peripheral blood of ovarian cancer patients was significantly higher than that of healthy controls[(77.4±8.12)% vs(. 64.19±9.7)%,P < 0.01]. After co-culture with SKOV3,the percentage of mTOR+ CD4 + Treg were elevated(P < 0.05),and the levels of mTOR signaling pathway related genes and proteins also increased. After inhibition of mTOR signal of CD4 + Treg in SKOV3 growth environment,the glucose uptake(193.49 ± 13.28 vs. 174.05 ± 14.58,P < 0.01)and glycolysis level(21.97±0.87 vs. 4.85±1.54,P < 0.001)were decreased significantly. Glucose metabolism - related genes and proteins were also significantly reduced. Conclusion:mTOR and its downstream signaling pathway are significantly activated in peripheral blood CD4 + Treg of ovarian cancer patients,and mTOR signaling pathway can affect glucose metabolism of CD4 + Treg by regulating glucose metabolist-related genes and protein levels.

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FU Xin, WU Ming, CHEN Xian, LIU Shuna, ZHANG Lei, LI Rong, XU Juan, TAO Ziqi, WANG Ting, WANG Fang. Role of mTOR signaling pathway in regulating CD4 + Treg glucose metabolism in ovarian cancer[J].,2023,(5):604-610.

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  • Received:December 13,2022
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  • Online: May 18,2023
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