纳布啡调节HIF-1α/VEGF信号通路对结直肠癌细胞活性和血管生成的影响  

Effects of nalbuphine on the activity and angiogenesis of colorectal cancer cells by regulating the HIF-1α/VEGF signaling pathway

作　　者：田园园 吴倍 王飞[1] 杨静[2] TIAN Yuan-yuan;WU Bei;WANG Fei;YANG Jing(Department of Anesthesiology,the No.2 Hospital of Baoding,Baoding 071051,China;Department of Colorectal Surgery,the No.2 Hospital of Baoding,Baoding 071051,China)

机构地区：[1]保定市第二医院麻醉科,河北保定071051 [2]保定市第二医院肛肠外科,河北保定071051

出　　处：《中国现代普通外科进展》2024年第10期760-765,共6页Chinese Journal of Current Advances in General Surgery

基　　金：保定市科技计划项目(2241ZF190)。

摘　　要：目的:探讨纳布啡(Nal)调节缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路对结直肠癌(CRC)细胞活性和血管生成的影响。方法:使用25~800μmol/L的Nal处理CRC细胞SW480,筛选最佳药物浓度;将SW480细胞分为对照组(Control组)、低浓度纳布啡组(Nal-L组,50μmol/L)、中浓度纳布啡组(Nal-M组,100μmol/L)、高浓度纳布啡组(Nal-H组,200μmol/L)、高浓度纳布啡(200μmol/L)+HIF-1α/VEGF信号通路激活剂组(Nal-H+DMOG组,200μmol/L的Nal+2mmol/LDM OG)。细胞平板克隆形成实验检测细胞增殖能力;流式细胞术检测细胞凋亡能力;划痕实验检测细胞迁移能力;Transwell法检测细胞侵袭能力;Western blot检测细胞的血管形成能力以及HIF-1α/VEGF信号通路蛋白表达情况。结果:Nal可以抑制SW480细胞增殖,呈浓度依赖性;与Control组比较,Nal-L组、Nal-M组、Nal-H组的克隆形成数目、侵袭细胞数、划痕愈合率、血管结构形成数及VEGF蛋白表达、HIF-1α蛋白表达下降,凋亡率增加(P<0.05);与Nal-H组比较,Nal-H+DM OG组克隆形成数目、划痕愈合率、侵袭细胞数、血管结构形成数、HIF-1α蛋白表达、VEGF蛋白表达显著升高(P<0.05),细胞凋亡率显著降低(P<0.05)。结论:Nal对CRC细胞增殖、迁移和侵袭以及血管结构形成的抑制作用,可能是通过抑制HIF-1α/VEGF信号通路发挥作用。Objective: To investigate the effects of nalbuphine (Nal) on the activity and an-giogenesis of colorectal cancer(CRC) cells by regulating the hypoxia inducible factor-1α(HIF-1α)/ vascular endothelial growth factor(VEGF) signaling pathway. Methods: CRC cell SW480 was treated with Nal of 25-800 μmol/L to screen for the optimal drug concentration;CRC cells were separated into Control group, low concentration nalbuphine group(Nal-L group, 50 μmol/L), me-dium concentration nalbuphine group(Nal-M group, 100 μmol/L), high concentration nalbuphine group(Nal-H group, 200 μmol/L), and high concentration nalbuphine(200 μmol/L) +HIF-1α/VEGF signaling pathway activator group(Nal-H+DMOG group, 200 μmol/L Nal+2 mM DMOG). The cell plate cloning experiment was applied to detect cell proliferation. The apoptotic ability of cells was evaluated by flow cytometry. The migration ability of cells was tested using scratch assay. The in-vasive ability of cells was measured using the Transwell method. The ability of cells to form blood vessels and the expression of HIF-1α/VEGF signaling pathway proteins were analyzed using Western blot. Results: Nal can inhibit cell proliferation in a concentration dependent manner. Compared with the Control group, the number of clone formation, scratch healing rate, number of invasive cells, number of vascular structure formation, HIF-1α, and VEGF protein expression in the Nal-L group, Nal-M group, and Nal-H group were greatly reduced(P<0.05), the apoptosis rate of cells was obviously increased(P<0.05). Compared with the Nal-H group, the number of clone formation, scratch healing rate, number of invasive cells, number of vascular structure formation, HIF-1α, and VEGF protein expression in the Nal-H+DMOG group were obviously increased(P< 0.05), the apoptosis rate of cells was greatly decreased(P<0.05). Conclusion: The inhibitory ef-fects of Nal on proliferation, migration, invasion, and vascular structure formation of CRC cells may be achieved by inhibiting the HIF-1α/VEGF signaling pathway.

关 键 词：结直肠肿瘤 纳布啡 缺氧诱导因子-1α/血管内皮生长因子信号通路 增殖 迁移 侵袭 血管生成 

分 类 号：R735.3[医药卫生—肿瘤]