基于Wnt5a信号通路探讨放射性^(125)I粒子组织间植入治疗胰腺癌的疗效及机制

Investigating the Efficacy and Mechanism of Interstitial Implantation of Radioactive ^(125)I Seeds for Pancreatic Cancer Treatment:Insights into the Wnt5a Signaling Pathway

目的基于Wnt5a信号通路探讨放射性^(125)I粒子组织间植入治疗胰腺癌的疗效及机制。方法(1)选取2020年1月~2021年12月吉林大学中日联谊医院行超声引导经皮穿刺组织学活检证实为胰腺癌,行超声引导放射性^(125)I粒子植入治疗的26例患者(26个病灶)作为研究对象。术后2个月CT观察肿瘤大小及空腹血糖的变化,通过免疫组织化学染色检测患者组织标本Wnt5a的表达。(2)通过GEPIA数据库分析179例胰腺癌组织和171例胰腺组织中Wnt5a的mRNA水平差异。(3)体外采用放射线照射胰腺癌Panc-1细胞,通过Western Blot及实时荧光定量PCR检测Wnt5a和线粒体氧化磷酸化复合体亚基的表达变化。结果在植入放射性125I粒子的26个病灶中有20个病灶明显减小,有效率为76.9%,胰腺癌肿瘤得到局部控制。患者术后空腹血糖明显升高,但仍在8.4~11.2 mmol/L范围内。GEPIA数据库的生物信息学分析发现,Wnt5a在胰腺癌组织中的表达明显高于正常组织(P<0.05)。免疫组织化学染色显示胰腺癌组织Wnt5a的表达显著高于癌旁组织。经放射线照射后,胰腺癌细胞Wnt5a的表达明显下调,三磷酸腺苷合酶6、细胞色素C氧化酶亚基4等线粒体氧化磷酸化复合体亚基的mRNA水平升高,而蛋白水平明显下降(P<0.05)。结论放射性125I粒子通过抑制胰腺癌细胞Wnt5a表达,降低线粒体氧化磷酸化复合体亚基翻译,抑制胰腺癌细胞的增殖。

Objective To explore the efficacy and mechanism of interstitial implantation of radioactive ^(125)I seeds for pancreatic cancer treatment:elucidating the role of the Wnt5a signaling pathway.Methods A cohort of 26 patients diagnosed with pancreatic cancer through percutaneous puncture biopsy under ultrasound guidance between January 2020 and December 2021 was enrolled in this study.These patients underwent treatment through the precise interstitial implantation of radioactive ^(125)I seeds,guided by ultrasound imaging.The efficacy of the treatment was assessed by monitoring tumor size changes using abdominal computerized tomography(CT)examination two months post-surgery.Additionally,fasting blood glucose(FBG)levels were evaluated.Furthermore,the expression of Wnt5a protein in patient biopsies was analyzed using immunohistochemical staining.To further investigate the involvement of the Wnt5a signaling pathway in pancreatic cancer,the differential mRNA expression of Wnt5a was analyzed in a comprehensive dataset comprising 179 pancreatic cancer cases and 171 adjacent normal pancreas tissues,using the GEPIA database.Moreover,in vitro experiments were conducted using Panc-1 cells,where the expression levels of Wnt5a and mitochondrial oxidative phosphorylation complex subunits were assessed using Western blotting and real-time quantitative PCR after radiation exposure.Results In the cohort of 26 patients,a remarkable reduction in the size of 20 lesions was observed,yielding an effective rate of 76.9%.This compelling outcome indicated that the interstitial implantation of radioactive 125I seeds achieved effective local control of pancreatic cancer tumors.Notably,post-surgery,the patients'FBG levels exhibited a significant increase,yet they remained within the range of 8.4 to 11.2 mmol/L.In line with these clinical findings,bioinformatics analysis unveiled a significantly higher expression of Wnt5a in pancreatic cancer tissues compared to normal tissues(P<0.05).Consistent with this,immunohistochemical staining demonstrated a pronounced elevation in the expression of Wnt5a in pancreatic cancer tissues compared to adjacent tissues.To elucidate the underlying mechanism,the in vitro experiments using Panc-1 cells revealed a significant downregulation of Wnt5a protein levels following radiotherapy.Furthermore,the mRNA expression levels of mitochondrial oxidative phosphorylation complex subunits,cytochrome c oxidase subunit 4(COX4)and ATP synthase 6(ATP6),were observed to increase,while the protein levels exhibited a significant decrease(P<0.05).Conclusion These findings elucidate the intricate mechanisms by which radioactive ^(125)I seed therapy hinders the proliferation of pancreatic cancer cells.Through the suppression of Wnt5a expression and the modulation of mitochondrial oxidative phosphorylation complex subunits,this approach holds promise as an effective therapeutic intervention for pancreatic cancer treatment.