Abstract

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-1cells induced by Nmethyl-N'-nitro-N-nitrosoguanidine (MNNG). GES-1cells were exposed to 1μmol/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-1cells by enhancing the Warburg effect during long-term exposure to NOCs.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.