Glutamine affects T24 bladder cancer cell proliferation by activating STAT3 through ROS and glutaminolysis.

Changes in metabolism are common phenomena in tumors. Glutamine (Gln) has been documented to play a critical role in tumor growth. In this study, we aimed to to explore the mechanisms through which bladder cancer cells utilize Gln to fulfill their biosynthetic needs during proliferation. In addition, the roles of Gln in the tricarboxylic acid (TCA) cycle, reactive oxygen species (ROS) regulation, and signal transducer and activator of transcription 3 (STAT3) expression were examined in vitro in the T24 bladder cancer cell line. The results revealed that the T24 cell line was markedly Gln‑dependent and that Gln supplementation promoted T24 proliferation through the actions of Gln as a ROS moderator and as a metabolic fuel in the TCA cycle. Importantly, extracellular Gln deprivation deregulated the production of the transcription factor, STAT3. Additionally, STAT3 expression was affected by the degree of Gln metabolism, as regulated by Gln intermediates and ROS. Thus, on the whole, the findings of this study demonstrate that Gln promotes the proliferation of the Gln‑dependent bladder cancer cell line, T24, by supplementing adenosine triphosphate (ATP) production and neutralizing ROS to activate the STAT3 pathway.