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Abstract
Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. However, the mechanism underlying its biological effects remains unclear. In this study, we investigated the inhibitory effect of NTP on the invasion of HeLa cells, and explored the possible mechanism. Our results showed that NTP exposure for 20 or 40 s significantly suppressed the migration and invasion of HeLa cells on the basis of matrigel invasion assay and wound healing assay, respectively. Moreover, NTP reduced the activity and protein expression of the matrix metalloproteinase (MMP)-9 enzyme. Western blot analysis indicated that NTP exposure effectively decreased phosphorylation level of both ERK1/2 and JNK, but not p38 MAPK. Furthermore, treatment with MAPK signal pathway inhibitors or NTP all exhibited significant depression of HeLa cells migration and MMP-9 expression. The result showed that NTP synergistically suppressed migration and MMP-9 expression in the presence of ERK1/2 inhibitor and JNK inhibitor, but not p38 MAPK inhibitor. Taken together, these findings suggested that NTP exposure inhibited the migration and invasion of HeLa cells via down-regulating MMP-9 expression in ERK1/2 and JNK signaling pathways dependent manner. These findings provide hints to the potential clinical research and therapy of NTP on cervical cancer metastasis.
Highlights
Non-thermal plasma (NTP), generated at room temperature by ionization of neutral gas molecules, results in a mixture of numerous short-lived but highly active chemical species[1]
Our results demonstrated that NTP exposure inhibited the migration and invasion of human cervical cancer HeLa cells via inhibiting mitogen-activated protein kinase (MAPK) signaling pathway, which led to down-regulation of matrix metalloproteinase (MMP)-9 activity and expression
The results suggested that inhibition of MMP-9 expression by NTP could be mediated through inactivation of ERK1/2 and Jun N-terminal kinase (JNK) signaling pathways in HeLa cells
Summary
Non-thermal plasma (NTP), generated at room temperature by ionization of neutral gas molecules, results in a mixture of numerous short-lived but highly active chemical species[1]. Metastasis occurs via a complex series of events, including invasion of cells from a primary tumor into the circulation system, immigration of these cells to distant organs, adhesion to endothelial cells, and infiltration into tissue[17,18] In this process, degradation of the extracellular matrix (ECM) is mainly performed by matrix metalloproteinases (MMPs)[19]. Our results demonstrated that NTP exposure inhibited the migration and invasion of human cervical cancer HeLa cells via inhibiting MAPK signaling pathway, which led to down-regulation of MMP-9 activity and expression. These findings provided a novel mechanistic insight into the potential of NTP on the suppression of cervical cancer invasion and metastasis
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