Salmonella typhimurium A1-R tumor targeting in immunocompetent mice is enhanced by a traditional Chinese medicine herbal mixture.
Salmonella typhimurium A1-R tumor targeting in immunocompetent mice is enhanced by a traditional Chinese medicine herbal mixture.
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发表时间：
2013-05
影响因子：
2
通讯作者：
Yong Zhang;N. Zhang;S. Su;R. Hoffman;Ming Zhao
中科院分区：
文献类型：
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作者：
Yong Zhang;N. Zhang;S. Su;R. Hoffman;Ming Zhao
我们已经开发了一种使用基因工程菌株鼠伤寒沙门氏菌A1-R（A1-R）的细菌癌症治疗策略。A1-R是亮氨酸和精氨酸的营养缺陷型，其减弱正常组织中的细菌生长，但允许高肿瘤毒力。A1-R在临床相关的裸鼠模型中对转移性人和鼠癌细胞系有效。然而，高剂量的A1-R治疗免疫活性小鼠模型中的肿瘤受到毒性的限制。目前的研究评估了一种传统的中药（TCM）草药混合物与A1-R治疗相结合的高侵袭性肺癌的同基因转移性免疫活性小鼠模型。在刘易斯肺癌模型中，中药混合物和S.鼠伤寒沙门氏菌A1-R使细菌能够安全地以2 × 10（7）菌落形成单位的大剂量每周一次i. v.给药，与A1-R单药治疗相比，疗效增加，毒性降低。草药混合物防止体重减轻，脾脏重量增加和A1-R引起的肝脏感染，以及皮肤，肝脏和脾脏上的出血性病变，所有这些都是在A1-R单药治疗中观察到的。本研究的结果表明，A1-R和TCM的组合具有重要的潜力，用于治疗高度侵袭性类型的癌症，包括那些对标准治疗有抵抗力的癌症。
We have developed a bacterial cancer therapy strategy using the genetically-engineered strain Salmonella typhimurium A1-R (A1-R). A1-R is auxotrophic for leu and arg which attenuates bacterial growth in normal tissue but allows high tumor virulence. A1-R is effective against metastatic human and murine cancer cell lines in clinically-relevant nude-mouse models. However, A1-R treatment of tumors in immunocompetent mouse models with high doses is limited by toxicity. The current study evaluated a traditional Chinese medicine (TCM) herbal mixture in combination with A1-R therapy in a syngeneic metastatic immunocompetent mouse model of highly aggressive lung cancer. In a model of Lewis lung carcinoma, the combination of a TCM herbal mixture and S. typhimurium A1-R enabled bacteria to be safely administered at the large dose of 2 × 10(7) colony forming units once a week i.v. with increased treatment efficacy and reduced toxicity compared to monotherapy with A1-R. The herbal mixture prevented body weight loss, spleen weight gain and liver infection by A1-R, as well as hemorrhagic lesions on the skin, liver, and spleen, all observed with A1-R monotherapy. The results of the present study suggest that the combination of A1-R and TCM has important potential for therapy of highly aggressive types of cancer, including those which are resistant to standard therapy.