Vector-Mediated Selective Expression of Lethal Factor, a Toxic Element of Bacillus Anthracis, Damages A549 Cells via Inhibition of MAPK and AKT Pathways

Wenlei Zhuo^1,✉, Guangli Tao², Liang Zhang³, Zhengtang Chen¹

1. Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China;
2. Department of Nephrology, Xinqiao Hospital, Third Military Medical University, Chongqing, China;
3. Department of Environmental Hygiene, College of Preventive Medicine, Third Military Medical University, Chongqing, China.

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Citation:
Zhuo W, Tao G, Zhang L, Chen Z. Vector-Mediated Selective Expression of Lethal Factor, a Toxic Element of Bacillus Anthracis, Damages A549 Cells via Inhibition of MAPK and AKT Pathways. Int J Med Sci 2013; 10(3):292-298. doi:10.7150/ijms.5570. Available from https://www.medsci.org/v10p0292.htm

Abstract

Lethal factor (LF), a major toxic element of Bacillus anthracis combined with its protective antigen (PA), enters the cells through the cytomembrane receptors and causes damage to the host cells, thereby leading to septicemia, toxemia, and meningitis with high mortality. LF has been identified as a potential biotech-weapon, which can impede cancer growth in vascular endothelial cells because of its cytotoxicity. However, the feasibility of LF application and further investigations has been limited because LF is nonspecific. To solve this problem, we constructed a vector that contained the LF sequence, which was regulated by a tumor-specific human telomerase reverse transcriptase promoter (hTERTp). Results showed that LF was selectively expressed in lung cancer A549 cells but not in normal cells, thereby resulting in A549 cell apoptosis. The results also revealed that the inhibition of mitogen-activated protein kinase and AKT pathways was partially involved in the process. Thus, hTERTp-regulated LF increase could be a promising approach in lung cancer-targeted therapy.

Keywords: Anthrax lethal factor, Selective expression, Targeted therapy, A549 cell, Signaling pathway.