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.
Highlights
Thyroid papillary carcinoma is one of the most common malignancies worldwide and generally shows indolent character [1]
non-thermal atmospheric pressure plasma (NTP) is a promising and emerging modality in cancer research, and we previously reported that the anti-cancer effects of NTP are mediated through a growth arrest and cell death [10,11]
Our data show that the plasma-treated thyroid cancer cells lost their flat, spindle-shaped horizontal polarization and had decreased cytosolic projections, which are important for cellular mobility and environmental sensing, whereas the cells did not show significant apoptosis by NTP treatment
Summary
Thyroid papillary carcinoma is one of the most common malignancies worldwide and generally shows indolent character [1]. It can sometimes be aggressive, with extracapsular spread, strap muscle, recurrent laryngeal nerve, and tracheal invasion, as well as metastasis to lymph nodes. NTPs have been reported to have anti-cancer activities in various tissues, including lung cancer [5], colorectal cancer [10,11,12], and melanoma [13], suggesting a new anti-tumor therapeutic modality. Our group previously showed that NTP induced a growth arrest and retarded tumor invasion in colorectal cancer cells [10,11]. The anti-cancer mechanism of NTP has mainly focused on apoptosis-related mechanisms with increased reactive oxygen species or redox imbalances [14]
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