Electrotransfer of Different Control Plasmids Elicits Different Antitumor Effectiveness in B16.F10 Melanoma

Cancers

Jaka Lavrencak¹  Maja Cemazar²  Tanja Jesenko²  Urska Kamensek²  Masa Bosnjak²  Gregor Sersa²  Loree Heller³ 

[1] Department of Cytopathology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia;Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia;Frank Reidy Research Center of Bioelectrics, Old Dominion University, 4211 Monarch Way, Norfolk, VA 23508, USA;

关键词: gene electrotransfer;    control plasmids;    murine melanoma tumor;    DNA sensors;    cytokines;    antitumor effectiveness;   

DOI  :  10.3390/cancers10020037

来源: DOAJ

【 摘 要 】

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were determined. GET of all three plasmids caused significant growth delay in melanoma tumors; nevertheless, the effect of pVAX1 was significantly greater than pControl. While DNA sensors in vivo were not upregulated significantly, cytokines IFN β and TNF α were upregulated after GET of pVAX1. In vitro, the mRNAs of some cytosolic DNA sensors were overexpressed after GET; however, with no significant difference among the three plasmids. In summary, although differences in antitumor effects were observed among control plasmids in vivo, no differences in cellular responses to plasmid GET were detected in tumor cells in vitro. Thus, the tumor microenvironment as well as some plasmid properties are most probably responsible for the antitumor effectiveness.

【 授权许可】

Unknown