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减毒鼠伤寒沙门氏菌调节肿瘤微环境代谢在肿瘤治疗中的应用研究

ttenuated Salmonella typhimurium regulates TME metabolism in tumor therapy

中文摘要英文摘要

目的:胰腺癌的发病率在全球呈逐年增加的趋势,且患者在5年生存率不足10%,给人类生命健康带来了严重威胁。胰腺癌是一种免疫细胞浸润贫瘠的"冷"肿瘤,免疫疗法对其治疗并无显著效果,探索新的胰腺癌治疗方法刻不容缓。本研究以减毒鼠伤寒沙门氏菌ppGpp为载体,设计了一种编码(半)胱氨酸水解酶(CGL)的工程菌株SLpCGL(plus)用于胰腺癌的治疗。方法:使用pBAD诱导表达系统,构建工程菌株SLpCGL(plus)。在体外实验中,使用结晶紫染色检测SLpCGL(plus)在体外对胰腺癌的抑制作用。结果:SLpCGL(plus)能显著抑制胰腺癌的生长。结论:本研究成功开发了一种基于减毒鼠伤寒沙门氏菌装载CGL蛋白靶向肿瘤微环境中(半)胱氨酸代谢,从而抑制胰腺癌肿瘤生长的方法,为胰腺癌的临床治疗提供了新的思路。

Objective: the incidence of pancreatic cancer is increasing year by year in the world, and the 5-year survival rate is less than 10%. Pancreatic cancer is a kind of"Cold" tumor with poor infiltration of immune cells. Immunotherapy has no significant effect on it, so it is urgent to explore a new therapy for pancreatic cancer. In this study, an engineered strain SLpCGL(plus) encoding cysteine hydrolase (CGL) was designed using attenuated Salmonella enterica ppGpp as a vector for the treatment of pancreatic cancer. Methods: the engineered strain SLpCGL(plus) was constructed with pBAD induced expression system. In vitro experiments, the inhibitory effect of SLpCGL(plus) on pancreatic cancer in vitro was examined using crystal violet staining.Results: SLpCGL(plus) significantly inhibited the growth of pancreatic cancer. Conclusion: In this study, we successfully developed a Salmonella enterica method to inhibit pancreatic cancer tumor growth by targeting cysteine metabolism in the tumor microenvironment. It provides a new idea for the clinical treatment of pancreatic cancer.

李忠英、郑金海

肿瘤学微生物学生物工程学

微生物学鼠伤寒沙门氏菌肿瘤代谢(半)胱氨酸胰腺癌(半)胱氨酸水解酶(CGL)

MicrobiologySalmonella typhimuriumTumor metabolismCyst(e)inePancreatic cancerCyst(e)ine hydrolase (CGL)

李忠英,郑金海.减毒鼠伤寒沙门氏菌调节肿瘤微环境代谢在肿瘤治疗中的应用研究[EB/OL].(2024-05-29)[2025-08-24].http://www.paper.edu.cn/releasepaper/content/202405-145.点此复制

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