Attenuated Salmonella engineered with an apoptosis-inducing factor (AIF) eukaryotic expressing system enhances its anti-tumor effect in melanoma in vitro and in vivo.

Attenuated Salmonella engineered with an apoptosis-inducing factor (AIF) eukaryotic expressing system enhances its anti-tumor effect in melanoma in vitro and in vivo. Appl Microbiol Biotechnol. 2020 Feb 24;: Authors: Wang H, Chen T, Wan L, Lu J, Wei H, Deng KY, Wei J, Xin HB Abstract VNP20009, an attenuated mutant of Salmonella, is potentially applied for tumor therapy due to its specific accumulation and proliferation in the hypoxic zone of tumor. However, studies have shown that human immunity system and the associated toxicities of attenuated Salmonella evidently alleviated the anti-tumor effect when tumor is reduced. As apoptosis-inducing factor (AIF) can directly induce nuclear apoptosis in the absence of caspases to avoid unwished apoptosis in normal cells, therefore, a eukaryotic expressing VNP20009-AbVec-Igκ-AIF (V-A-AIF) strain was constructed in the present study, and its anti-melanoma effects were evaluated in vitro and in vivo. The results showed that AIF expressed by the V-A-AIF strain significantly enhanced the apoptosis of B16F10 cells in vitro, seen as remarkable decrease of tumor volume, formation of larger necrotic areas, and prolongation of the lifespan in a melanoma-bearing mouse model. Furthermore, we observed that the colonization of the V-A-AIF strain and the massive expression of AIF in tumors significantly promoted apoptosis of tumor cells by upregulating the expression ratio of Bcl-2-associated X protein/B ...
Source: Applied Microbiology and Biotechnology - Category: Microbiology Authors: Tags: Appl Microbiol Biotechnol Source Type: research