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阿糖胞苷-顺铂-依托泊苷化疗联合贝伐珠单抗通过抑制肿瘤侵袭和血管生成调节神经胶质瘤进展。

Combination of Ad-SGE-REIC and bevacizumab modulates glioma progression by suppressing tumor invasion and angiogenesis.

机构信息

Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Department of Neurosurgery, Hamamatsu University School of Medicine, Shizuoka, Japan.

出版信息

PLoS One. 2022 Aug 25;17(8):e0273242. doi: 10.1371/journal.pone.0273242. eCollection 2022.

DOI:10.1371/journal.pone.0273242
PMID:36006934
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9409598/
Abstract

Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab. Ad-SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad-SGE-REIC, as well as decreased β-catenin protein levels. In malignant glioma mouse models, overall survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing the angiogenesis and invasion of tumors. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.

摘要

REIC/Dkk-3（REIC/Dkk-3）在永生化细胞中的表达减少是一种肿瘤抑制因子，其过表达已被证明在许多人类癌症中作为治疗靶基因发挥抗肿瘤作用。最近，我们证明了携带 REIC/Dkk-3 的腺病毒载体在超级基因表达系统（Ad-SGE-REIC）中具有抗神经胶质瘤作用。抗血管内皮生长因子治疗（如贝伐单抗）在胶质母细胞瘤患者中显示出令人信服的治疗优势。然而，贝伐单抗并没有改善新诊断的胶质母细胞瘤患者的总生存率。在这项研究中，我们研究了 Ad-SGE-REIC 对接受贝伐单抗治疗的神经胶质瘤的影响。Ad-SGE-REIC 治疗导致用贝伐单抗治疗的侵袭细胞数量显著减少。Western blot 分析显示，在用贝伐单抗和 Ad-SGE-REIC 治疗的细胞中，几种内质网应激标志物的表达增加，β-连环蛋白蛋白水平降低。在恶性神经胶质瘤小鼠模型中，联合治疗组的总生存期延长。这些结果表明，Ad-SGE-REIC 和贝伐单抗的联合治疗通过抑制肿瘤的血管生成和侵袭发挥抗神经胶质瘤作用。联合使用 Ad-SGE-REIC 和贝伐单抗可能是治疗恶性神经胶质瘤的一种有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/2691678e9662/pone.0273242.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/37071ce4b777/pone.0273242.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/b196baa7d84f/pone.0273242.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/4a7be7f89b97/pone.0273242.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/175371541916/pone.0273242.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/2691678e9662/pone.0273242.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/37071ce4b777/pone.0273242.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/b196baa7d84f/pone.0273242.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/4a7be7f89b97/pone.0273242.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/175371541916/pone.0273242.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f56/9409598/2691678e9662/pone.0273242.g005.jpg

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