Clinical Laboratory, Taizhou People's Hospital Affiliated to Nantong University, Taizhou, Jiangsu 225300, China.
Oncology Department, Taizhou People's Hospital Affiliated to Nantong University, Taizhou, Jiangsu 225300, China.
Anal Cell Pathol (Amst). 2018 May 3;2018:8941908. doi: 10.1155/2018/8941908. eCollection 2018.
Our previous findings showed a good therapeutic effect of the combination of suicide gene HSV-TK, nuclide 131I, and magnetic fluid hyperthermia (MFH) on hepatoma by using magnetic nanoparticles as linkers, far better than any monotherapy involved, with no adverse effects. This combination therapy might be an eligible strategy to treat hepatic cancer. However, it is not clear how the combination regimen took the therapeutic effects. In the current study, to explore the possible mechanisms of radionuclide-gene therapy combined with MFH to treat hepatoma at tissue, cellular, and molecular levels and to provide theoretical and experimental data for its clinical application, we examined the apoptosis induction of the combination therapy and investigated the expression of the proteins related to apoptosis such as survivin, livin, bcl-2, p53, and nucleus protein Ki67 involved in cell proliferation, detected VEGF, and MVD involved in angiogenesis of tumor tissues and analyzed the pathologic changes after treatment. The results showed that the combination therapy significantly induced the hepatoma cell apoptosis. The expression of survivin, VEGF, bcl-2, p53, livin, Ki67, and VEGF proteins and microvascular density (MVD) were all decreased after treatment. The therapeutic mechanisms may be involved in the downregulation of Ki67 expression leading to tumor cell proliferation repression and inhibition of survivin, bcl-2, p53, and livin protein expression inducing tumor cell apoptosis, negatively regulating VEGF protein expression, and reducing vascular endothelial cells, which results in tumor angiogenesis inhibition and microvascular density decrease and tumor cell necrosis. These findings offer another basic data support and theoretical foundation for the clinical application of the combination therapy.
我们之前的研究结果表明，将自杀基因 HSV-TK、核素 131I 和磁性流体热疗（MFH）与磁性纳米颗粒作为连接物结合使用，对肝癌具有良好的治疗效果，远远优于任何单一治疗方法，且无不良反应。这种联合治疗可能是治疗肝癌的一种合适策略。然而，目前尚不清楚联合治疗方案如何发挥治疗效果。在本研究中，为了在组织、细胞和分子水平上探讨放射性核素-基因联合 MFH 治疗肝癌的可能机制，为其临床应用提供理论和实验依据，我们检测了联合治疗的诱导细胞凋亡作用，并研究了与细胞增殖相关的蛋白 survivin、livin、bcl-2、p53、核蛋白 Ki67 的表达，检测了肿瘤组织中与血管生成相关的 VEGF 和 MVD，并分析了治疗后的病理变化。结果表明，联合治疗能显著诱导肝癌细胞凋亡。治疗后 survivin、VEGF、bcl-2、p53、livin、Ki67 和 VEGF 蛋白的表达以及微血管密度（MVD）均降低。其治疗机制可能涉及下调 Ki67 表达，从而抑制肿瘤细胞增殖，抑制 survivin、bcl-2、p53 和 livin 蛋白表达，诱导肿瘤细胞凋亡，负性调节 VEGF 蛋白表达，减少血管内皮细胞，从而抑制肿瘤血管生成和降低微血管密度，导致肿瘤细胞坏死。这些发现为该联合治疗的临床应用提供了另一个基础数据支持和理论依据。
