Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
Key Laboratory of Urinary System Diseases, Qingdao, Shandong 266003, P.R. China.
Int J Mol Med. 2019 Dec;44(6):2189-2200. doi: 10.3892/ijmm.2019.4385. Epub 2019 Oct 25.
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.
代谢变化是肿瘤中的常见现象。谷氨酰胺 (Gln) 已被证明在肿瘤生长中发挥关键作用。在这项研究中，我们旨在探索膀胱癌细胞在增殖过程中利用 Gln 来满足其生物合成需求的机制。此外，还在 T24 膀胱癌细胞系中研究了 Gln 在三羧酸 (TCA) 循环、活性氧 (ROS) 调节和信号转导和转录激活因子 3 (STAT3) 表达中的作用。结果表明，T24 细胞系明显依赖 Gln，Gln 补充通过 Gln 作为 ROS 调节剂和 TCA 循环中的代谢燃料的作用促进 T24 增殖。重要的是，细胞外 Gln 剥夺会使转录因子 STAT3 的产生失调。此外，STAT3 表达受 Gln 代谢程度的影响，受 Gln 中间产物和 ROS 调节。因此，总的来说，这项研究的结果表明，Gln 通过补充三磷酸腺苷 (ATP) 的产生和中和 ROS 来激活 STAT3 通路，促进 Gln 依赖性膀胱癌细胞系 T24 的增殖。
