Directorate of Veterinary Medicine, Luxor, Egypt.
Department of Microbiology, Faculty of Veterinary Medicine, Cairo, Egypt.
Exp Cell Res. 2021 Feb 1;399(1):112423. doi: 10.1016/j.yexcr.2020.112423. Epub 2020 Dec 15.
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，可以通过激活宿主免疫系统和逆转免疫抑制性肿瘤微环境来消退肿瘤。本研究旨在探讨沙门氏菌 Typhimurium ATCC 14028 的外膜囊泡（ST-OMVs）的抗肿瘤活性，分别在体外人结直肠癌细胞（HTC116）、乳腺癌细胞（MCF-7）和肝癌细胞（HepG2）系和体内艾氏腹水癌荷瘤小鼠模型中进行研究，无论是作为单一免疫疗法还是作为常用常规化疗的佐剂。此外，我们还研究了 ST-OMVs 的安全性。用移植艾氏腹水癌的成年瑞士白化雌性小鼠分别用 ST-OMVs、紫杉醇或两者联合治疗。分析肿瘤体积、生长抑制率、Bax 和 VEGF 基因表达的定量 RT-PCR、组织病理学和 caspase-3、Beclin-1、CD49b 和 Ki-67 的免疫表达。我们的结果表明，ST-OMVs 显著降低了肿瘤体积，显著提高了肿瘤生长抑制率，上调了 caspase-3、Beclin-1 和 CD49b 的免疫组织化学表达（增强了 NK 细胞的募集）。此外，ST-OMVs 下调了 Ki-67 的表达，增加了 Bax 基因的表达，降低了 qRT-PCR 分析检测到的 VEGF 基因的表达。组织学上，ST-OMVs 促进了细胞凋亡，减少了肿瘤侵袭和有丝分裂活性。此外，ST-OMVs 对各种体外研究的癌细胞系表现出显著的细胞毒性活性。我们的研究结果表明，ST-OMVs 具有潜在的抗肿瘤活性，可作为一种有前途的安全抗肿瘤免疫疗法或作为常规化疗药物的佐剂，解决其部分问题。
