Department of Urology, XiangYa Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Neoplasma. 2022 Dec;69(6):1396-1405. doi: 10.4149/neo_2022_220626N665.
Stanniocalcin1 (STC1) is a secreted glycoprotein, which is highly expressed in prostate cancer cells. However, the biological functions of STC1 in modulating ferroptosis and glycolysis in prostate cancer are still not clear. The viability of PC-3 and DU145 cells was detected by CCK-8 assay. The relative Fe2+ level was detected by an Iron Assay Kit. MDA level was detected by Lipid Peroxidation MDA Assay Kit. Glucose uptake and lactate product were measured by Glycolysis Assay Kit and Lactate Assay Kit. In this study, STC1 was highly expressed in prostate cancer tissue specimens and cells. STC1 knockdown suppressed prostate cancer cell proliferation, and upregulated Fe2+ level, reduced glutathione (GSH) level, downregulated GPX4 and SLC7A11 protein expressions in PC-3 cells and DU145 cells. Besides, STC1 knockdown decreased glucose uptake, lactate product, and ATP level, as well as downregulated glycolysis-related protein HK2 and LDHA protein expressions. In addition, STC1 knockdown repressed the Nrf2/HO-1/NQO1 pathway. Nrf2 pathway activator, Oltipraz, upregulated Nrf2, total NQO1, and HO-1 expressions in PC-3 cells and DU145 cells. Moreover, Nrf2 pathway activator Oltipraz reversed the effect of STC1 knockdown on Fe2+ level and GPX4, SLC7A11, HK2, LDHA protein expressions in PC-3 cells and DU145 cells. Finally, STC1 knockdown restrained the tumor volume, tumor weight, and glycolysis in prostate cancer in vivo. Thus, STC1/Nrf2 pathway is a vital pathway to induce ferroptosis and suppress glycolysis in prostate cancer.
斯钙素 1(STC1)是一种分泌型糖蛋白,在前列腺癌细胞中高度表达。然而,STC1 在调节前列腺癌中的铁死亡和糖酵解中的生物学功能尚不清楚。通过 CCK-8 法检测 PC-3 和 DU145 细胞的活力。用铁测定试剂盒检测相对 Fe2+水平。用脂质过氧化 MDA 测定试剂盒检测 MDA 水平。用糖酵解测定试剂盒和乳酸测定试剂盒测定葡萄糖摄取和乳酸产物。在这项研究中,STC1 在前列腺癌组织标本和细胞中高表达。STC1 敲低抑制前列腺癌细胞增殖,并上调 PC-3 细胞和 DU145 细胞中的 Fe2+水平,降低谷胱甘肽(GSH)水平,下调 GPX4 和 SLC7A11 蛋白表达。此外,STC1 敲低降低葡萄糖摄取、乳酸产物和 ATP 水平,并下调糖酵解相关蛋白 HK2 和 LDHA 蛋白表达。此外,STC1 敲低抑制 Nrf2/HO-1/NQO1 通路。Nrf2 通路激活剂 Oltipraz 上调 PC-3 细胞和 DU145 细胞中的 Nrf2、总 NQO1 和 HO-1 的表达。此外,Nrf2 通路激活剂 Oltipraz 逆转了 STC1 敲低对 PC-3 细胞和 DU145 细胞中 Fe2+水平和 GPX4、SLC7A11、HK2、LDHA 蛋白表达的影响。最后,STC1 敲低抑制了前列腺癌体内的肿瘤体积、肿瘤重量和糖酵解。因此,STC1/Nrf2 通路是诱导前列腺癌中铁死亡和抑制糖酵解的重要通路。