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Δευτέρα 31 Μαΐου 2021

Silencing of kallikrein-related peptidase 6 attenuates the proliferation, migration, and invasion of gastric cancer cells through inhibition of epithelial-mesenchymal transition

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Exp Ther Med. 2021 Jul;22(1):770. doi: 10.3892/etm.2021.10202. Epub 2021 May 17.

ABSTRACT

Kallikrein-related peptidase 6 (KLK6), a member of the kallikrein-related peptidase family, is involved in the regulation of epithelial-mesenchymal transition (EMT) in cancer cells and is highly expressed in gastric cancer tissues. The aim of the present study was to investigate the effect of KLK6 on the proliferation, migration and invasion of gastric cancer cells and to determine the underlying mechanism of its actions. The expression of KLK6 was measured in metastatic gastric cancer cells using western blotting and reverse transcription-quantitative PCR, and KLK6 was overexpressed or inhibited in HGC-27 cells using plasmid transfection. Cell proliferation, migration, invasion and EMT were also evaluated using Cell Counting Kit 8, Transwell and western blot analysis, respectively. In addition, a mouse xenograft model was constructed by injection of HGC-27 cells. The xenograft was treated with KLK6 interference or overexpression plasmids to study the in vivo effects of KLK6 on tumor development. The results demonstrated that KLK6 was highly expressed in HGC-27 cells and that KLK6 inhibition attenuated cell proliferation, migration and invasion and prevented gastric cancer tumor development. In addition, KLK6 inhibition reduced the expression of epithelial cell adhesion molecule and vimentin, reduced the phosphorylation of SMAD2 and SMAD3 and upregulated epithelial-cadherin expression. In conclusion, KLK6 inhibition suppressed the proliferation, migration and invasion of gastric cancer cells both in vitro and in vivo through the inhibition of EMT. These findings indicate that KLK6 a potential therapeutic target for gastric cancer therapy.

PMID:34055069 | PMC:PMC8145264 | DOI:10.3892/etm.2021.10202

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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