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KMID : 1140120110160030238
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Cancer Prevention Research
2011 Volume.16 No. 3 p.238 ~ p.248
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Inhibition of Cell Invasion by Bojungikgigilkyung-tang in Human Lung Cancer A549 Cells
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Bae Jong-Hoon
Shin Dong-Yeok
Park Cheol
Park Sang-Eun
Hong Sang-Hoon
Park Dong-Il
Choi Yung-Hyun
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Abstract
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Bojungikkigamikilkyung-tang (BJIKTP), a traditional korean herbal formulation, has been used for patients suffering from a lung disease in oriental medicine. However, the molecular mechanisms underlying BJIKTP-induced anti-invasiveness and anti-metastasis have not been thoroughly studied. In the present study, we investigated the effects of BJIKTP on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human lung cancer A549 cells. It was found that low concentrations of BJIKTP were not cytotoxic effects, whereas high concentrations of BJIKTP could inhibit the cell proliferation as determined by MTT assay. Within the concentrations which were not cytotoxic effects, BJIKTP markedly inhibited the cell motility and invasiveness in a dose-dependent manner. The anti-invasive activity of BJIKTP was found to be associated with increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance (TER). The activities of matrix metalloproteinase (MMP)-2 and -9 in A549 cells were dose-dependently inhibited by treatment with BJIKTP, and this was correlated with a decrease in expression of their mRNA and proteins, and up-regulation of tissue inhibitors of metalloproteinases (TIMPs) expression. Additionally, BJIKTP repressed the levels of the claudin family members, which are major components of TJs that play a key role in control and selectivity of paracellular transport. Furthermore, the levels of E-cadherin, a type I transmembrane glycoprotein, and snail, an epithelial to mesenchymal transitionregulator and zinc finger transcription factor, were markedly inhibited by BJIKTP treatment. Taken together, these findings suggest that TJs and MMPs are critical targets of BJIKTP-induced anti-metastasis in human lung cancer A549 cells.
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KEYWORD
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BJIKTP, A549, Anti-metastasis, TJs, MMPs
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