应用遗传改造的沙门菌介导肿瘤治疗的研究进展

Advances in tumor-therapy using genetically modified Salmonella

摘要:

肿瘤是机体在各种致瘤因子作用下，局部组织细胞异常增生所形成的赘生物。肿瘤治疗一直是临床上的一个难题，而放疗、化疗和手术等常规的肿瘤治疗方法均具有明显的局限性。早期研究发现某些厌氧菌或兼性厌氧菌具有抗肿瘤效应，例如兼性厌氧菌鼠伤寒沙门氏菌可以通过某些机制选择性定殖于肿瘤并抑制肿瘤生长，其应用于肿瘤治疗具有许多潜在的优势。过去的一二十年里，已有不少研究者通过遗传操作减弱沙门菌毒力，提高其定殖肿瘤的靶向性，或以减毒沙门菌作为载体向肿瘤靶向递呈各种治疗分子，并在许多动物试验中观察到遗传改造沙门菌的良好抗肿瘤效应。随着沙门菌抗肿瘤研究的不断深入，应用遗传改造的沙门菌有希望成为一条更有效的肿瘤治疗途径。本文将从沙门菌的抗肿瘤机制、遗传改造的沙门菌介导肿瘤治疗的研究进展和目前研究存在的问题等方面进行综述。

Abstract:

Tumor is a neoplasm formed by the abnormal proliferation of local tissue cells under the effects of different tumorigenic factors. Tumor-therapy has always been a difficult clinical issue, while regular cancer treatments, such as radiotherapy, chemotherapy and surgery, have obvious limitations. Earlier studies have shown that some obligate anaerobes or facultative anaerobes have anti-tumor effects, for example, Salmonella typhymurium as facultative anaerobic bacteria can selectively colonize tumors and inhibit their growth. Besides, Salmonella has many advantages in tumor-therapy. In the past decade or two, many researchers have carried out genetic manipulation to attenuate the virulence of Salmonella, to improve their specificity of tumor colonization and specially to use attenuated Salmonella as carriers to deliver a variety of anti-tumor therapeutic molecules, and these genetically modified Salmonella have shown good anti-tumor effects in many animal experiments. Along with further research of Salmonella-mediated antitumor treatment, applications of genetically modified Salmonella for more effective tumor-therapy are promising. We reviewed the anti-tumor mechanisms of Salmonella, the research progress in tumor-therapy using genetically modified Salmonella, and current problems and possible solutions.