RESUMEN
N-nitroso compounds (NOCs) exposure is a major risk factor for the development of gastric cancer. However, the carcinogenic mechanisms by which NOCs induce gastric and other cancers, especially the NOCs-induced Warburg effect, have not been comprehensively studied. Lactate dehydrogenase (LDH), which has two subunits (LDHA and LDHB), plays an important role in the Warburg effect of tumor cells. Therefore, we hypothesized that LDHA and LDHB could promote Warburg effect in malignant transformed GES-1 cells induced by Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). GES-1 cells were exposed to 1 µmol/L MNNG and cultured for 40 passages. During the culturing process, cell proliferation, migration, and soft agar colony formation significantly increased after 30 passages. Following MNNG exposure, lactate, LDH, glucose uptake, and the expression levels of key enzymes in glycolysis were significantly increased. Knocking down LDHA or LDHB alone reduced lactate secretion, inhibited cell viability, and impaired migratory capacities. Knocking down LDHA and LDHB together fully suppressed lactate secretion and effectively suppressed the malignant phenotype of cells transformed by long-term MNNG exposure. Finally, we demonstrated that overexpression of LDHA and LDHB promotes the malignant transformation of GES-1 cells by enhancing the Warburg effect during long-term exposure to NOCs.
RESUMEN
The purpose of this meta-analysis was to evaluate the relationship between serum 25-hydroxyvitamin D[25(OH)D] levels and gastric cancer. PubMed, Embase, Cochrane Library, Web of Science, The China Academic Journals full-text database, Wanfang Database of Chinese Academic Journals, VIP Chinese Science and Technology Periodicals database, and Chinese Biomedical Literature database were systematically searched. Case-control studies on the correlation between serum 25-hydroxyvitamin D levels and gastric cancer were retrieved, and the data extracted were analyzed. The results of 9 case-control studies containing 671 patients showed that serum 25(OH)D levels in the gastric cancer group were lower than those in the control group (weighted mean difference (WMD) = -8.90, 95% confidence interval (CI): -11.5, -6.32, p < 0.01); the risk of vitamin D deficiency in the gastric cancer group was higher than that in the control group (Odds ratio = 3.09, 95% CI: 1.96, 4.87, p < 0.01). The serum 25(OH)D levels in patients with well and moderately differentiated gastric cancer were higher than those in patients with poorly differentiated gastric cancer (WMD = -3.58, 95% CI: -6.41, -0.74, p = 0.01). Thus, low levels of vitamin D may increase the risk of gastric cancer. Systematic review registration: PROSPERO CRD42022327942.
