Ning Bo-Tao, Yu Bin, Chan Shing, Chan Jian-Liang, Huang Jian-Dong, Chan Godfrey Chi-Fung
Pediatric Intensive Care Unit, Shanghai Children's medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Department of Peadiatrics & Adolescent, Queen Mary Hospital, LKS Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong SAR, PR China.
J Cancer. 2017 Jun 3;8(9):1609-1618. doi: 10.7150/jca.18776. eCollection 2017.
Neuroblastoma is an embryonic solid tumor derived from the progenitors of the sympathetic nervous system. More than half of the patients developed metastatic disease at the time of initial diagnosis and had poor outcome with current therapeutic approaches. In recent years, some obligate and facultative anaerobic bacteria were reported to target the hypoxic and necrotic region of solid tumor models and caused tumor regression. We recently successfully constructed an "obligate" anaerobic strain YB1 that was applied in breast cancer nude mice model by us. Here, we report the application of YB1 in neuroblastoma treatment. The anti-cancer effect and side-effects of YB1 was examined in both and experiment. Previous established orthotopic neuroblastoma SCID/beige murine model using SK-NLP/luciferase cell line was adopted. , YB1 induced apoptosis for up to 31.4% of the neuroblastoma cells under anaerobic condition, three times more than that under aerobic condition (10.9%). The expression of both Toll like Receptor 4 and 5 (TLR4 and TLR5) in cancer cells were significantly up-regulated (<0.05<0.01 respectively) after the treatment of YB1 under anaerobic condition. In mouse model, YB1 preferentially accumulated inside the core of the tumors, rather than in normal tissues as our previous reported. This is suggestive of the hypoxic nature of tumor core. Tumor growth was significantly retarded in YB1 treatment group (). Furthermore, there was no long-term organ damage noted in all the organs examined including heart, lung, liver, spleen and brain in the YB1 treated mice. The genetic modified strain YB1 is a promising anti-tumor strategy against the tumor bulk for neuroblastoma. Future study can be extended to other common cancer types to verify the relative efficacy on different neoplastic cells.
神经母细胞瘤是一种源自交感神经系统祖细胞的胚胎性实体瘤。超过半数的患者在初次诊断时已发生转移性疾病，并且采用当前的治疗方法其预后较差。近年来，有报道称一些专性和兼性厌氧菌靶向实体瘤模型的缺氧和坏死区域并导致肿瘤消退。我们最近成功构建了一种“专性”厌氧菌株YB1，并将其应用于我们建立的乳腺癌裸鼠模型。在此，我们报告YB1在神经母细胞瘤治疗中的应用。在体外和体内实验中均检测了YB1的抗癌效果和副作用。采用先前建立的使用SK-NLP/荧光素酶细胞系的原位神经母细胞瘤SCID/米色小鼠模型。在厌氧条件下，YB1诱导高达31.4%的神经母细胞瘤细胞凋亡，是有氧条件下（10.9%）的三倍。在厌氧条件下用YB1处理后，癌细胞中Toll样受体4和5（TLR4和TLR5）的表达均显著上调（分别为<0.05和<0.01）。在小鼠模型中，YB1优先聚集在肿瘤核心内部，而不像我们先前报道的那样聚集在正常组织中。这表明肿瘤核心具有缺氧特性。在YB1治疗组中肿瘤生长显著减缓（）。此外，在接受YB1治疗的小鼠中，在包括心脏、肺、肝脏、脾脏和大脑在内的所有检查器官中均未发现长期器官损伤。基因改造菌株YB1是一种针对神经母细胞瘤肿瘤主体的有前景的抗肿瘤策略。未来的研究可以扩展到其他常见癌症类型，以验证其对不同肿瘤细胞的相对疗效。
