Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang Province, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health (23618504), Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang Province, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Ministry of Health (23618504), Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
Life Sci. 2024 Nov 15;357:123109. doi: 10.1016/j.lfs.2024.123109. Epub 2024 Oct 9.
This study aims to explore the inhibitory effect of selenium on cervical cancer through suppression of glucose metabolic reprogramming and its underlying mechanisms.
Sodium selenite (SS) treated HeLa and SiHa cells were assessed for proliferation using the CCK-8 assay and immunofluorescence. DNA synthesis was measured with the EdU assay. A nude mouse xenograft model evaluated SS's anti-cervical cancer effects. Reactive oxygen species (ROS) and mitochondrial membrane potential were measured using flow cytometry, DCFH-DA, and JC-1 probes, respectively. Apoptosis was detected via Annexin V/PI staining and Western blot. Glucose uptake, lactate production, and ATP generation were determined using 2-NBDG probes and assay kits. The mRNA and protein levels of glycolysis-related genes HK2, GLUT1, and PDK1 were measured using RT-qPCR and Western blot.
SS inhibited HeLa and SiHa cells viability in a dose- and time-dependent manner. Intraperitoneal injection of SS in nude mice significantly inhibited HeLa cell xenograft growth without evident hepatotoxicity or nephrotoxicity. SS inhibited glucose metabolic reprogramming in cancer cells primarily via ROS-mediated AKT/mTOR/HIF-1α pathway inhibition. Pretreatment with N-acetylcysteine (NAC) or MHY1485 (an mTOR activator) partially reversed the inhibitory effects of SS on glucose metabolic reprogramming, cell proliferation, and migration, as well as its pro-apoptotic effects.
SS exhibited anti-cervical cancer effects, likely through the induction of ROS generation and inhibition of glucose metabolic reprogramming in cervical cancer cells, thereby inhibiting cell proliferation and promoting apoptosis. These findings provide new insights into understanding the molecular mechanisms underlying SS for potential new drug development for cervical cancer.
本研究旨在通过抑制葡萄糖代谢重编程来探索硒对宫颈癌的抑制作用及其潜在机制。
用 CCK-8 法和免疫荧光法检测亚硒酸钠（SS）处理的 HeLa 和 SiHa 细胞的增殖。用 EdU 法测定 DNA 合成。裸鼠异种移植模型评估 SS 对宫颈癌的抑制作用。用流式细胞术、DCFH-DA 和 JC-1 探针分别测量活性氧（ROS）和线粒体膜电位。通过 Annexin V/PI 染色和 Western blot 检测细胞凋亡。用 2-NBDG 探针和试剂盒测定葡萄糖摄取、乳酸生成和 ATP 生成。用 RT-qPCR 和 Western blot 测定糖酵解相关基因 HK2、GLUT1 和 PDK1 的 mRNA 和蛋白水平。
SS 呈剂量和时间依赖性抑制 HeLa 和 SiHa 细胞活力。腹腔注射 SS 显著抑制裸鼠 HeLa 细胞异种移植生长，无明显肝毒性或肾毒性。SS 主要通过 ROS 介导的 AKT/mTOR/HIF-1α 通路抑制抑制癌细胞葡萄糖代谢重编程。用 N-乙酰半胱氨酸（NAC）或 MHY1485（mTOR 激活剂）预处理部分逆转了 SS 对葡萄糖代谢重编程、细胞增殖和迁移的抑制作用以及其促凋亡作用。
SS 对宫颈癌具有抑制作用，可能是通过诱导宫颈癌细胞中 ROS 的产生和抑制葡萄糖代谢重编程，从而抑制细胞增殖并促进细胞凋亡。这些发现为深入了解 SS 对宫颈癌的作用机制提供了新的见解，为开发治疗宫颈癌的新药提供了新的思路。
