1. Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
Int J Med Sci. 2013 Sep 21;10(12):1639-48. doi: 10.7150/ijms.6960. eCollection 2013.
An effective cancer therapeutic should target tumours specifically with limited systemic toxicity. Here, we transformed an attenuated Salmonella typhimurium (S. typhimurium) with an Apoptin expressing plasmid into a human laryngeal carcinoma cell line. The expression of the inserted gene was measured using fluorescence and immunoblotting assays. The attenuated S. typhimurium-mediated Apoptin significantly decreased cytotoxicity and strongly increased cell apoptosis through the activation of caspase-3. The process was mediated by Bax, cytochrome c and caspase-9. A syngeneic nude murine tumour model was used to determine the anti-tumour effects of the recombinant bacteria in vivo. Systemic injection of the recombinant bacteria with and without re-dosing caused significant tumour growth delay and reduced tumour microvessel density, thereby extending host survival. Our findings indicated that the use of recombinant Salmonella typhimurium as an Apoptin expression vector has potential cancer therapeutic benefits.
有效的癌症治疗方法应该具有靶向肿瘤的特异性,同时具有有限的全身毒性。在这里,我们将表达凋亡素的质粒转化入减毒鼠伤寒沙门氏菌(S. typhimurium),构建成一株人喉癌细胞系。通过荧光和免疫印迹实验检测插入基因的表达。减毒鼠伤寒沙门氏菌介导的凋亡素通过激活 caspase-3 显著降低了细胞毒性,并强烈增加了细胞凋亡。该过程通过 Bax、细胞色素 c 和 caspase-9 介导。我们使用同基因裸鼠肿瘤模型在体内确定了重组细菌的抗肿瘤作用。重组细菌的全身注射和再给药均导致显著的肿瘤生长延迟,并降低了肿瘤微血管密度,从而延长了宿主的生存时间。我们的研究结果表明,使用重组鼠伤寒沙门氏菌作为凋亡素表达载体具有潜在的癌症治疗益处。