一氧化氮在鼠伤寒沙门氏菌介导的癌细胞杀伤中的作用。
Role of nitric oxide in Salmonella typhimurium-mediated cancer cell killing.
机构信息
Department of Microbiology and Immunology, Sherman Fairchild Science Building, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA.
出版信息
BMC Cancer. 2010 Apr 17;10:146. doi: 10.1186/1471-2407-10-146.
BACKGROUND
Bacterial targeting of tumours is an important anti-cancer strategy. We previously showed that strain SL7838 of Salmonella typhimurium targets and kills cancer cells. Whether NO generation by the bacteria has a role in SL7838 lethality to cancer cells is explored. This bacterium has the mechanism for generating NO, but also for decomposing it.
METHODS
Mechanism underlying Salmonella typhimurium tumour therapy was investigated through in vitro and in vivo studies. NO measurements were conducted either by chemical assays (in vitro) or using Biosensors (in vivo). Cancer cells cytotoxic assay were done by using MTS. Bacterial cell survival and tumour burden were determined using molecular imaging techniques.
RESULTS
SL7838 generated nitric oxide (NO) in anaerobic cell suspensions, inside infected cancer cells in vitro and in implanted 4T1 tumours in live mice, the last, as measured using microsensors. Thus, under these conditions, the NO generating pathway is more active than the decomposition pathway. The latter was eliminated, in strain SL7842, by the deletion of hmp- and norV genes, making SL7842 more proficient at generating NO than SL7838. SL7842 killed cancer cells more effectively than SL7838 in vitro, and this was dependent on nitrate availability. This strain was also ca. 100% more effective in treating implanted 4T1 mouse tumours than SL7838.
CONCLUSIONS
NO generation capability is important in the killing of cancer cells by Salmonella strains.
背景
细菌靶向肿瘤是一种重要的抗癌策略。我们之前曾表明，鼠伤寒沙门氏菌 SL7838 株可靶向并杀死癌细胞。细菌产生的 NO 是否在 SL7838 对癌细胞的致死作用中发挥作用尚待探讨。该细菌具有生成 NO 的机制，但也具有分解 NO 的机制。
方法
通过体外和体内研究探讨了鼠伤寒沙门氏菌肿瘤治疗的机制。通过化学分析（体外）或使用生物传感器（体内）进行了 NO 测量。使用 MTS 进行了癌细胞细胞毒性测定。通过分子成像技术测定细菌细胞存活和肿瘤负担。
结果
SL7838 在厌氧细胞悬浮液中、在体外感染的癌细胞中和在活小鼠植入的 4T1 肿瘤中生成了一氧化氮（NO），最后，使用微传感器进行了测量。因此，在这些条件下，NO 生成途径比分解途径更活跃。在 SL7842 株中，通过缺失 hmp 和 norV 基因消除了后者，使得 SL7842 比 SL7838 更擅长生成 NO。SL7842 在体外比 SL7838 更有效地杀死癌细胞，这依赖于硝酸盐的可用性。与 SL7838 相比，该菌株在治疗植入的 4T1 小鼠肿瘤方面的效果也提高了约 100%。
结论
NO 生成能力对沙门氏菌株杀伤癌细胞很重要。
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