Non-thermal atmospheric pressure plasma inhibits thyroid papillary cancer cell invasion via cytoskeletal modulation, altered MMP-2/-9/uPA activity.

Abstract

Plasma, the fourth state of matter, is defined as a partially or completely

ionized gas that includes a mixture of electrons and ions. Advances in plasma

physics have made it possible to use non-thermal atmospheric pressure plasma

(NTP) in cancer research. However, previous studies have focused mainly on

apoptotic cancer cell death mediated by NTP as a potential cancer therapy. In

this study, we investigated the effect of NTP on invasion or metastasis, as well

as the mechanism by which plasma induces anti-migration and anti-invasion

properties in human thyroid papillary cancer cell lines (BHP10-3 and TPC1). Wound

healing, pull-down, and Transwell assays demonstrated that NTP reduced cell

migration and invasion. In addition, NTP induced morphological changes and

cytoskeletal rearrangements, as detected by scanning electron microscopy and

immunocytochemistry. We also examined matrix metalloproteinase (MMP)-2/-9 and

urokinase-type plasminogen activator (uPA) activity using gelatin zymography, uPA

assays and RT-PCR. FAK, Src, and paxillin expression was detected using Western

blot analyses and immunocytochemistry. NTP decreased FAK, Src, and paxillin

expression as well as MMP/uPA activity. In conclusion, NTP inhibited the invasion

and metastasis of BHP10-3 and TPC1 cells by decreasing MMP-2/-9 and uPA

activities and rearranging the cytoskeleton, which is regulated by the FAK/Src

complex. These findings suggest novel actions for NTP and may aid in the

development of new therapeutic strategies for locally invasive and metastatic

cancers.