Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with regard to mortality and prognosis, and the 5-year survival rate for all patients diagnosed with ESCC remains poor. A better understanding of the biological mechanisms of ESCC tumorigenesis and progression is of great importance to improve treatment of this disease. In this study, we demonstrated that the glutathione metabolism pathway is highly enriched in ESCC cells compared with normal esophageal epithelial cells in an in vivo mouse model. In addition, treatment with L-buthionine-sulfoximine (BSO) to deplete glutathione decreased the ESCC tumor burden in mice, thus demonstrating the critical role of glutathione metabolism in ESCC progression. BSO treatment also led to decreased cell proliferation and activation of cell apoptosis in ESCC. Finally, BSO treatment blocked NF-κB pathway activation in ESCC. Our study reveals a new pathway that regulates ESCC progression and suggests that inhibition of glutathione metabolism may be a potential strategy for ESCC treatment.
Animals ; Apoptosis ; Carcinogenesis ; Carcinoma, Squamous Cell ; Cell Proliferation ; Epithelial Cells ; Esophageal Neoplasms* ; Glutathione* ; Humans ; Metabolism* ; Mice ; Mortality ; Prognosis ; Survival Rate ; Tumor Burden

Objective:To investigate the expression levels of peripheral blood lymphocytes in patients with high-grade squamous intraepithelial lesions (HSIL) of the cervix and early cervical cancer, and to analyze their correlation with the clinicopathological characteristics of cervical cancer.Methods:The clinical data of 65 patients with HSIL and 78 patients with early cervical cancer (2018 International Federation of Gynecology and Obstetrics stage ≤ stage Ⅱ A) treated in Shanxi Province Cancer Hospital from October 2020 to November 2021 were retrospectively analyzed, and 31 healthy people undergoing physical examination during the same period were treated as the healthy control group. The expressions of CD3 + T cells, CD4 + T cells, CD8 + T cells, NK cells, NK/T cells and other immune cells in fasting peripheral blood of the patients were detected by using flow cytometry. Results:The expression levels of CD3 + T cells, CD4 + T cells, CD4 +/CD8 + and NK cells were 71±8, 39±7, 1.5±0.5, 16±7, respectively in HSIL group, and 73±9, 41±9, 1.5±0.6, 16±9, respectively in early cervical cancer group, which were lower than those in the healthy control group (76±9, 45±10, 2.0±1.3, 20±7) (all P < 0.05). The expression levels of CD8 + T cells was 28±7, 29±8, respectively in HSIL group and early cervical cancer group, which were higher than those in the healthy control group (24±7) (all P < 0.05). The expression level of total B cells in early cervical cancer group was lower than that in healthy control group (10±4 vs.12±3, P < 0.05). The expression level of CD3 + T cells in peripheral blood of early cervical cancer patients with tumor diameter >4 cm and nerve/vascular invasion was 71±10 and 72±8, which was lower than that of patients with tumor diameter 2-4 cm, ≤2 cm and without nerve/vascular invasion (72±8, 75±8, 78±7); the expression level of CD8 + T cell was 32±8 and 35±4, which was higher than that of patients with tumor diameter 2-4 cm, ≤2 cm, and without nerve/vascular invasion (28±8, 28±7, 29±8) (all P < 0.05). The levels of CD3 + T cells and total B cells were negatively correlated with the tumor diameter (all P < 0.05), while the level of CD8 + T cells was positively correlated with tumor diameter ( P < 0.05); the levels of CD3 + T cells and NK cells were negatively correlated with nerve/vascular invasion (all P < 0.05). Conclusions:The immune function of the body starts to change in the early progression of cervical cancer, and is related to the tumor diameter and nerve/vascular invasion of cervical cancer.