title: Non-thermal plasma inhibits human cervical cancer HeLa cells invasiveness by suppressing the MAPK pathway and decreasing matrix metalloproteinase-9 expression.
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.
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei, 230031, Anhui Province, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong.
authors.forename: K N
authors.initials: KN
authors.lastname: Yu
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei, 230031, Anhui Province, P.R. China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Bao
authors.affiliation: Institute of Plasma Physics, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei, 230031, Anhui Province, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Institute of Plasma Physics, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei, 230031, Anhui Province, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, 350 Shushanhu Road, Hefei, 230031, Anhui Province, P.R. China.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
mesh_terms: D002465:Cell Movement; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D058626:Plasma Gases
chemical_list: D009363:Neoplasm Proteins; D058626:Plasma Gases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
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