Nano-sized Gram-negative bacterial outer membrane vesicles possess unique structural and immunostimulatory effects that could be exploited to regress tumors by alerting the host immune system and reversing the immunosuppressive tumor microenvironment. The current study was conducted to investigate the antitumor activity of the outer membrane vesicles (ST-OMVs) of Salmonella Typhimurium ATCC 14028, in vitro in human colorectal carcinoma (HTC116), breast cancer (MCF-7), and hepatocellular carcinoma (HepG2) cell lines and in vivo in Ehrlich solid carcinoma-bearing mice model either as a mono-immunotherapy or as an adjuvant to a commonly used conventional chemotherapy. In addition, we investigated the safety of ST-OMVs. Adult Swiss albino female mice with transplanted Ehrlich solid carcinoma were treated with either ST-OMVs, paclitaxel or a combination of both. Tumor volume, growth inhibition rate, quantitative RT-PCR of Bax and VEGF genes expression, histopathology and immune-expression of caspase-3, Beclin-1, CD49b and Ki-67 were all analyzed. Our results showed that ST-OMVs significantly decreased tumor volume, significantly increased tumor growth inhibition rate, up-regulated the immunohistochemical expression of caspase-3, Beclin-1, and CD49b (enhanced recruitment of NK cells). Furthermore, ST-OMVs down-regulated the expression of Ki-67, increased Bax gene expression and decreased VEGF gene expression as detected by qRT-PCR analysis. Histologically, ST-OMVs promoted apoptosis, decreased tumor invasion and mitotic activities. Moreover, ST-OMVs showed a remarkable cytotoxic activity in various investigated in vitro cancer cell lines. Our findings demonstrate potential antitumor activity of ST-OMVs that might be used as a promising safe antitumor immunotherapy or an adjuvant to conventional chemotherapeutic drugs, resolving some of their problems.

纳米级革兰氏阴性细菌外膜囊泡具有独特的结构和免疫刺激作用，可以通过警告宿主免疫系统和逆转免疫抑制肿瘤的微环境来消退肿瘤。目前的研究以调查所述外膜囊泡（的抗肿瘤活性小号的T-OMV的）沙门氏菌鼠伤寒沙门氏菌ATCC 14028，在体外在人结肠直肠癌（HTC116），乳腺癌（MCF-7），和肝细胞癌（肝癌Ehrlich实体癌小鼠模型中的细胞系和体内模型，作为单一免疫疗法或作为常用常规化学疗法的佐剂。另外，我们调查了S的安全性T-OMV。用S T-OMVs，紫杉醇或两者结合治疗成年的瑞士白化病雌性小鼠，其移植了埃里希实体癌。分析了肿瘤体积，生长抑制率，Bax和VEGF基因表达的定量RT-PCR，caspase-3，Beclin-1，CD49b和Ki-67的组织病理学和免疫表达。我们的研究结果表明，小号T-OMV的显著降低肿瘤体积，增加显著肿瘤生长抑制率，上调的caspase-3的免疫组化表达，自噬基因Beclin 1，和CD49b（增强NK细胞的募集）。此外，小号T-OMV的下调中Ki-67的表达，增加的Bax的基因表达和通过qRT-PCR分析所检测的降低VEGF基因的表达。从组织学上S T-OMV促进细胞凋亡，减少肿瘤浸润和有丝分裂活动。此外，小号T-OMV的显示，各种研究的显着细胞毒活性在体外癌细胞系。我们的发现证明了S T-OMVs的潜在抗肿瘤活性，可以用作有前途的安全抗肿瘤免疫疗法或常规化学治疗药物的佐剂，解决了它们的一些问题。