RESUMO
OBJECTIVE： To study the effects of ivermectin on the migration and invasion of human gastric cancer cell lines BGC-823 and MGC-803 and its mechanism. METHODS： After treated with 0， 2.5， 5， 10， 20， 40 μmol/L ivermectin for 24 h， inhibitory rate of human gastric cancer cell lines BGC-823 and MGC-803 were detected by MTT assay. Effects of 5 μmol/L ivermectin and phosphate buffercontaining 0.67‰ dimethyl sulfoxide （control group） for 24 h on the migration and invasion of` gastric cancer cells BGC-823 and MGC-803 were observed by Transwell chamber invasion assay.Western blot assay was used to detect the protein expression of TGF-β1， TGF-βR， Smad2 and Smad3 in epithelial-mesenchymal transition （EMT） markers E-cadherin， N-cadherin， Vimentin， Snail and EMT transduction pathway TGF-β/smad of BGC-823 and MGC-803 cells after treated with 5， 10 μmol/L ivermectin and phosphate buffercontaining 0.67‰ dimethyl sulfoxide （control group） for 24 h. RESULTS： Ivermectin could inhibit the growth of BGC-823 and MGC-803， inhibitory rate of it was positively correlated with its concentration. Compared with control group， the number of migration and invasion BGC-823 and MGC-803 cells were decreased significantly after treated with 5 μmol/L ivermectin （P＜0.01 or P＜0.001）； the expression of E-cadherin protein was enhanced significantly in BGC-823 and MGC-803 cells after treated with 5 and 10 μmol/L ivermectin （P＜0.05 or P＜0.01 or P＜0.001）； the protein expression of N-cadherin， Vimentin， Snail， TGF-βR， Smad2 and Smad3 were decreased significantly （P＜0.05， P＜0.01 or P＜0.001）； protein expression of TGF-β1 was decreased significantly after treated with 10 μmol/L ivermectin （P＜0.05）. CONCLUSIONS： Ivermectin can significantly inhibit the migration and invasion of gastric cancer cells BGC-823 and MGC-803， and inhibiting the biological activity of EMT by reducing the expression of TGF-β/smad pathway is one of the mechanisms that inhibit the migration and invasion of gastric cancer cells.
RESUMO
OBJECTIVE: To screen the best combination of extractum of Robinia-living trametes and chemotherapy and investigate the action mechanism of Robinia-living trametes against the apoptosis of human gastric cancer cell MGC803. METHODS: MGC803 Cells were treated with different concentrations of Robinia-living trametes and chemotherapy drugs (5-Fu and paclitaxel) in vitro. The inhibitory rate of cells was measured by MTT assay. Morphological changes were observed with inverted microscope. The apoptosis rate of MGC803 cells which were treated with combination of Robinia-living trametes (0.2 mg·mL-1) and 5-Fu (2.5 μg·mL-1) was detected by FCM. The protein expression of P53 and p-Akt in MGC803 cells which were treated with combination of Robinia-living trametes (0.2 mg·mL-1) and 5-Fu (2.5 μg·mL-1) was detected by Western blot. RESULTS: The viability of MGC803 cells was reduced by Robinia-living trametes and chemotherapy drugs (5-Fu and paclitaxel) in a concentration- and time-dependent manner (P<0.01). Under reverse microscopy, cell body shrinking, nuclear pyrosis, and nuclear fragmentation were observed. The higher concentration, the longer treatment time, the more cells died. Compared with monotherapy, the combination of Robinia-living trametes and chemotherapy could reduce the survival rate of MGC803 cells. The protein expressions of P53 in MGC803 cells treated with combination of drugs was up-regulated, while that of P-Akt was down-regulated. CONCLUSION: The apoptosis of MGC803 cells in vitro may be induced by the inhibitory effect of the combination of Robinia-living trametes and 5-Fu on PI3K/Akt signaling pathway. Combination therapy of Robinia-living trametes and 5-Fu is potentially more effective in inhibition of tumor cells than monotherapy of Robinia-living trametes.