Bifidobacterium breve as a delivery vector of IL-24 gene therapy for head and neck squamous cell carcinoma in vivo
Bifidobacterium breve as a delivery vector of IL-24 gene therapy for head and neck squamous cell carcinoma in vivo
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短双歧杆菌作为IL-24基因治疗体内头颈鳞状细胞癌的递送载体
DOI：
10.1038/gt.2017.74
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发表时间：
2017-11-01
期刊：
影响因子：
5.1
通讯作者：
Guo, C.
中科院分区：
文献类型：
--
作者：
Wang, L.;Vuletic, I.;Guo, C.
有益细菌正在成为越来越流行的体内缺氧肿瘤靶向基因传递方法。本研究探讨了表达白细胞介素（IL）-24基因的重组短双歧杆菌新菌株（B. breve-IL24）对小鼠头颈部肿瘤异种移植的治疗作用。简而言之，通过电转化获得短双歧杆菌转化体。在不同时间点（细菌注射后1、3和7天）体内分析细菌肿瘤靶向能力。进一步分析细菌对体内肿瘤细胞的治疗作用：将30只皮下肿瘤Balb/c裸鼠随机分为三组（药物组、绿色荧光蛋白（GFP）组和生理盐水组）。治疗持续2周，药物组经尾静脉注射B. breve-IL24，GFP组注射B. breve-GFP，Saline组注射磷酸盐缓冲盐水。使用标准卡尺技术监测肿瘤生长，同时通过实时正电子发射断层扫描/计算机断层扫描（PET/CT）成像（[18F]-ML-10示踪剂）分析体内细胞凋亡诱导。实验结束时，收集肿瘤组织并通过蛋白质印迹进行分析。简而言之，我们的结果表明我们的新重组细菌具有体内靶向肿瘤组织的能力。至于治疗效果，我们的新菌株已被证明是一种有前途的体内肿瘤生长治疗方法。简而言之，与GFP组和盐水组相比，药物组观察到更高的肿瘤生长抑制和更高的肿瘤细胞凋亡诱导。总之，一种新的重组菌株短双歧杆菌-IL24为体内肿瘤治疗提供了一种新颖、安全且临床可接受的治疗方法。
Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia-tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing interleukin (IL)-24 gene (B. breve-IL24) on head and neck tumor xenograft in mice. Briefly, B. breve transformants were obtained through electro-transformation. Bacteria-tumor-targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post-bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, green fluorescent protein (GFP) group and Saline group). The therapy lasted for 2 weeks and included B. breve-IL24 administration via tail vein for Drug group, B. breve-GFP for GFP group and phosphate buffered saline for Saline group. The tumor growth was monitored using standard caliper technique, while the apoptosis induction in vivo was analyzed by Real-time Positron Emission Tomography/Computed Tomography (PET/CT) imaging ([18F]-ML-10 tracer). At the end of the experiment, tumor tissues were collected and analyzed by western blotting. Briefly, our results suggested that our new recombinant bacterium has the capability of targeting tumor tissue in vivo. As for the therapeutic effect, our new strain has revealed to be a promising therapeutic approach against tumor growth in vivo. Briefly, higher tumor growth inhibition and higher tumor cell apoptosis induction were observed in Drug group compared with the GFP and Saline groups. To conclude, a new recombinant strain B. breve-IL24 offers a novel, safe and clinically acceptable therapeutic approach for tumor therapy in vivo.