Antineoplastic activity of Salmonella Typhimurium outer membrane nanovesicles
Antineoplastic activity of Salmonella Typhimurium outer membrane nanovesicles
复制标题
DOI：
10.1016/j.yexcr.2020.112423
复制
发表时间：
2021-02-01
影响因子：
3.7
通讯作者：
Ata, Nagwa S.
中科院分区：
文献类型：
--
作者：
Aly, Rasha G. O.;El-Enbaawy, Mona I. H.;Ata, Nagwa S.
纳米尺寸的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微环境来使肿瘤消退。本研究旨在研究鼠伤寒沙门氏菌ATCC 14028的外膜囊泡（ST-OMV）在体外对人结肠直肠癌（HTC 116）、乳腺癌（MCF-7）、和肝细胞癌（HepG 2）细胞系中，以及在体内携带埃利希实体癌的小鼠模型中，免疫疗法或作为常用常规化疗的佐剂。此外，我们还研究了ST-OMV的安全性。用ST-OMV、紫杉醇或两者的组合治疗具有移植的埃利希实体癌的成年瑞士白化病雌性小鼠。观察肿瘤体积、生长抑制率、Bax和VEGF基因表达、组织病理学改变以及caspase-3、Beclin-1、CD 49 b和Ki-67的免疫组化表达。我们的研究结果表明，ST-OMV显著减小肿瘤体积，显著增加肿瘤生长抑制率，上调caspase-3，Beclin-1和CD 49 b的免疫组化表达（增强NK细胞的募集）。qRT-PCR分析显示，ST-OMV可下调Ki-67表达，上调Bax基因表达，下调VEGF基因表达。在组织学上，ST-OMV促进细胞凋亡，降低肿瘤侵袭和有丝分裂活性。此外，ST-OMV在各种研究的体外癌细胞系中显示出显著的细胞毒活性。我们的研究结果表明，ST-OMV可能被用作一种有前途的安全的抗肿瘤免疫治疗或辅助常规化疗药物，解决他们的一些问题的潜在抗肿瘤活性。
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, upregulated 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.