Inhibition of Tumor Growth and Metastasis by a Combination of Escherichia coli-mediated Cytolytic Therapy and Radiotherapy
Inhibition of Tumor Growth and Metastasis by a Combination of Escherichia coli-mediated Cytolytic Therapy and Radiotherapy
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DOI：
10.1038/mt.2009.295
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发表时间：
2010-03-01
影响因子：
12.4
通讯作者：
Min, Jung-Joon
中科院分区：
文献类型：
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作者：
Jiang, Sheng-Nan;Phan, Thuy X.;Min, Jung-Joon
我们曾报道，在静脉注射给荷瘤小鼠后，大肠杆菌K-12在缺氧和坏死的肿瘤区域定植。在这项研究中，我们建立了一种新的癌症治疗策略，使用工程菌来增强辐射的治疗效果。利用工程菌K-12产生溶细胞素A(ClyA)，并在原发肿瘤模型和转移肿瘤模型中评价其对肿瘤生长的影响。单独使用表达大肠杆菌的ClyA治疗一开始(治疗后9天)可显著降低肿瘤生长速度；然而，此后肿瘤倾向于生长。单纯放疗(RT；21GY)，肿瘤生长速度减慢，但不影响肿瘤大小。表达大肠杆菌的ClyA与放射[总共5×10(7)个集落形成单位(CFU)和21Gy射线]的联合治疗导致小鼠肿瘤显著缩小，甚至完全消失。此外，表达大肠杆菌ClyA的治疗显著抑制了小鼠转移性肿瘤的生长，延长了小鼠的生存时间。结果表明，工程菌治疗可显著提高放射治疗效果，对肺转移瘤的发生有显著的抑制作用。
We have reported that Escherichia coli K-12 colonizes hypoxic and necrotic tumor regions after intravenous injection into tumor-bearing mice. In this study, we established a novel strategy for cancer therapy using engineered bacteria to enhance the therapeutic effects of radiation. E. coli strain K-12 was engineered to produce cytolysin A (ClyA), and its effects on tumor growth in primary and metastatic tumor models were evaluated. A single treatment with E. coli-expressing ClyA significantly decreased tumor growth rates initially (9 days after treatment); however, the tumors tended to grow thereafter. With only radiotherapy (RT; 21 Gy), the tumor growth rates were retarded, but not the tumor sizes. A combination of therapy with E. coli-expressing ClyA and radiation [a total of 5 x 10(7) colony-forming units (CFU) and 21 Gy] resulted in significant tumor shrinkage and even complete disappearance of tumors in mice with tumors derived from murine CT26 colon cancer. Furthermore, treatment with E. coli-expressing ClyA markedly suppressed metastatic tumor growth and prolonged the survival time in mice. The results described here indicate that therapy with engineered E. coli could significantly improve the results of RT, and could exert a striking inhibitory effect on the development of lung metastasis.