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Modulation of Salmonella Tumor-Colonization and Intratumoral Anti-angiogenesis by Triptolide and Its Mechanism
Theranostics ( IF 12.4 ) Pub Date : 2017-06-01 , DOI: 10.7150/thno.18816
Jianxiang Chen , Yiting Qiao , Bo Tang , Guo Chen , Xiufeng Liu , Bingya Yang , Jing Wei , Xiangyu Zhang , Xiawei Cheng , Pan Du , Wenhui Jiang , Qingang Hu , Zi-Chun Hua

The weakened tumour colonization of attenuated Salmonella has severely hampered its clinical development. In this study, we investigated whether an anti-inflammation and antiangiogenesis compound triptolide could improve the efficacy of VNP20009, a highly attenuated Salmonella strain, against mice melanoma. By comparing the effects of conventional VNP20009 monotherapy and a combination therapy that uses both triptolide and VNP20009, we found that triptolide significantly improved the tumour colonization of VNP20009 by reducing the number of infiltrated neutrophils in the melanoma, which led to a larger necrotic area in the melanoma. Moreover, the combination therapy suppressed tumour angiogenesis by reducing the expression of VEGF in a synergistic manner, retarding the growth of the melanoma. Our study revealed that triptolide could significantly enhance the antitumour effect of VNP20009 by modulating tumour angiogenesis and the host immune response, providing a new understanding of the strategy to improve Salmonella-mediated tumour therapy.

中文翻译:

雷公藤内酯醇对沙门氏菌肿瘤定殖和肿瘤内抗血管生成的调节作用及其机制

减毒沙门氏菌的肿瘤定植减弱严重地阻碍了其临床发展。在这项研究中,我们研究了抗炎和抗血管生成复合雷公藤甲素是否可以提高高度减毒的沙门氏菌VNP20009的疗效。株,抗小鼠黑色素瘤。通过比较常规VNP20009单一疗法和同时使用雷公藤内酯醇和VNP20009的联合疗法的效果,我们发现雷公藤内酯醇通过减少黑素瘤中浸润的嗜中性白细胞数目显着改善了VNP20009的肿瘤定植,从而导致了更大的坏死面积。黑色素瘤。此外,联合疗法通过协同降低VEGF的表达,抑制黑素瘤的生长来抑制肿瘤血管生成。我们的研究表明雷公藤甲素可以通过调节肿瘤血管生成和宿主免疫反应来显着增强VNP20009的抗肿瘤作用,从而为改善沙门氏菌介导的肿瘤治疗策略提供了新的认识。
更新日期:2017-08-02
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