索拉菲尼对肾癌细胞的抑制作用与STC-1调控细胞内钙稳态的关系研究  

Relationship between the Inhibitory Effect of Sorafenib on Renal Cancer Cells and the Regulation of Intracellular Calcium Homeostasis by STC-1

作　　者：沈亚楠 谷江 张永春 罗浩鸣 Shen Yanan;Gu Jiang;Zhang Yongchun(The Affiliated Hospital of Guizhou Medical University,Guizhou 550000,China)

机构地区：[1]贵州医科大学附属医院泌尿外科,贵阳550000 [2]贵州省武警总队医院,贵阳550000 [3]兴义市人民医院,562400

出　　处：《医学研究杂志》2021年第6期98-101,97,共5页Journal of Medical Research

基　　金：贵州省科技厅社会攻关计划项目[黔科合sy字(2011)3060]。

摘　　要：目的探讨索拉菲尼对肾癌细胞抑制效应与斯钙素蛋白1(STC-1)调控细胞内钙稳态之间的关系,以期寻找逆转肾癌细胞耐药性的新途径。方法分别以0、1.25、2.5、5、10、20、40μmol/L索拉非尼干预肾癌细胞,按浓度依次递增进行分组,MTT法检测肾癌细胞增殖情况;RT-PCR方法及ELLSA法检测各组细胞STC-1的基因及蛋白表达;荧光分光光度法检测各组细胞内钙离子含量;化学比色法测定各组细胞Ca^(2+)-ATP酶活性。结果随着索拉菲尼浓度的递增,出现10μmol/L的浓度转折点,细胞抑制率及Ca^(2+)含量由逐渐升高趋向平稳,Ca^(2+)-ATP酶活性由逐渐下降趋向平稳,STC-1基因及蛋白表达逐渐升高。结论STC-1可能是肾癌细胞恶性增殖的保护因素,其可能通过调控Ca^(2+)水平,降低Ca^(2+)-ATP酶活性,使肾癌细胞内线粒体能量代谢活跃,促进肾癌细胞适应缺氧环境,从而对索拉菲尼产生抵抗作用。Objective To explore the relationship between the inhibitory effect of sorafenib on renal cell carcinoma cells and the regulation of intracellular calcium homeostasis by STC-1,so as to find a new way to reverse drug resistance of renal cell carcinoma cells.Methods Sorafenib was used to intervene renal cancer cells at concentrations of 0,1.25,2.5,5,10,20 and 40μmol/L,and groups were grouped according to increasing concentrations.The proliferation of renal cancer cells was detected by MTT method.RT-PCR method and ELLSA method was used to detect the gene and protein expression of STC-1 in each group of cells.Fluorescence spectrophotometry was used to detect the calcium ion content in each group of cells;chemical colorimetry was used to determine the activity of Ca^(2+)-ATPase in each group of cells.Results With the increasing concentration of sorafenib,a concentration turning point of 10μmol/L appeared.The cell inhibition rate and Ca^(2+)content gradually increased to stabilize,the Ca^(2+)-ATPase activity gradually decreased to stabilize,and the STC-1 gene and Protein expression gradually increased.Conclusion STC-1 may be a protective factor for the malignant proliferation of renal cancer cells.STC-1 may regulate the level of Ca^(2+),reduce the activity of Ca^(2+)-ATPase,activate the energy metabolism of mitochondria in renal cancer cells,and promote the adaptation of renal cancer cells to hypoxia,so as to produce resistance to Solafeni.

关 键 词：索拉菲尼 肾癌 STC-1 CA^(2+) 

分 类 号：R737.11[医药卫生—肿瘤]