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喜树碱联合载药微球经动脉化疗栓塞术在兔VX2肝癌模型中的实验研究

Experimental study of camptothecin combined with drug-eluting bead transarterial chemoembolization in the rabbit VX2 liver tumor model.

作者信息

Meng Fanguang, Li Yuyao, Liu Qian, Sun Liwei, Wang Hankang, Li Xiaodong, Li Guijie, Chen Feng

机构信息

Department of Radiology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Abdominal Medicine Imaging, Jinan, China.

Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.

出版信息

Front Oncol. 2022 Oct 10;12:906971. doi: 10.3389/fonc.2022.906971. eCollection 2022.

Abstract

Drug-eluting bead transarterial chemoembolization (DEB-TACE) has been widely used in the treatment of liver cancer; however, the utilization rate of chemotherapeutic drugs after embolization is low. Chemotherapy resistance mediated by high nuclear factor E2-related factor 2 (NRF2) expression limits DEB-TACE efficacy. Camptothecin (CPT), an NRF2 inhibitor, exerts chemosensitizing effects. We designed a controlled experiment to determine the efficacy and feasibility of DEB-TACE combined with CPT for the treatment of rabbit VX2 hepatoma. DEB-TACE activated NRF2 expression in the tumor region. NRF2 activation could be inhibited by the combined use of CPT. After DEB-TACE alone, the tumor necrosis was incomplete, there were still highly active tumor residues, and the apparent diffusion coefficient (ADC) value, which was negatively correlated with tumor activity observed by magnetic resonance imaging, remained low. After DEB-TACE combined with CPT, the relative necrosis of the tumor was more complete, the ADC value was higher, and the ADC change was greater. The single application of CPT did not result in evident liver function and physical burden to the rabbits. The combined use of CPT and DEB-TACE did not significantly increase DEB-TACE imaging of liver function and body. In conclusion, CPT can also inhibit high NRF2 expression after DEB-TACE treatment. Combining CPT with DEB-TACE can improve the sensitivity of DEB-TACE in the treatment of VX2 tumors, improve the therapeutic effect, and has no evident toxic and side effects. This study explored the methods for enhancing the efficacy of DEB-TACE in liver cancer from a new perspective and performed model experiments, which provided a theoretical basis for future clinical treatment.

摘要

载药微球经动脉化疗栓塞术(DEB-TACE)已广泛应用于肝癌治疗;然而,栓塞后化疗药物的利用率较低。由高核因子E2相关因子2(NRF2)表达介导的化疗耐药限制了DEB-TACE的疗效。喜树碱(CPT)作为一种NRF2抑制剂,具有化学增敏作用。我们设计了一项对照实验,以确定DEB-TACE联合CPT治疗兔VX2肝癌的疗效和可行性。DEB-TACE激活了肿瘤区域的NRF2表达。联合使用CPT可抑制NRF2的激活。单独进行DEB-TACE后,肿瘤坏死不完全,仍有高活性的肿瘤残留,且磁共振成像观察到的与肿瘤活性呈负相关的表观扩散系数(ADC)值仍较低。DEB-TACE联合CPT后,肿瘤的相对坏死更完全,ADC值更高,且ADC变化更大。单独应用CPT未给兔子带来明显的肝功能和身体负担。CPT与DEB-TACE联合使用未显著增加DEB-TACE对肝功能和身体的影像影响。总之,CPT还可抑制DEB-TACE治疗后的高NRF2表达。CPT与DEB-TACE联合使用可提高DEB-TACE对VX2肿瘤的治疗敏感性,提高治疗效果,且无明显毒副作用。本研究从新的角度探索了提高DEB-TACE治疗肝癌疗效的方法并进行了模型实验,为未来的临床治疗提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/529c/9590107/490abe9f6d0b/fonc-12-906971-g001.jpg

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