Scutellarin Reverses Cisplatin Resistance in Lung Cancer A549/DDP Cells by Down-regulation of c-met Expression
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Graphical Abstract
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Abstract
OBJECTIVE To explore the anti-resistance effects of scutellarin on cisplatin(DDP) resistance lung cancer A549/DDP cells and its reversal mechanism. METHODS MTT method was used to detect the reversing multiple of DDP-resistant lung cancer cell line A549/DDP, and cell toxicity, drug-resistant multiple of scutellarin on it; the colony formation assay was performed to determine the effect of scutellarin on the formation of A549/DDP cell clones; Western blotting was used to detect the expression of c-met protein expression in A549/DDP cells treated with scutellarin. RESULTS The result of MTT test showed that the resistance of DDP-resistance cell line A549/DDP was 5.77 times higher than in parent cell A549, the differences were statistically significant(P<0.01). Meanwhile, the protein expression level of c-met was higher in A549/DDP cell line than in A549(P<0.01). When scutellarin concentration was 20, 40, 80 and 160 μmol·L-1, its inhibition rates on DDP-resistant cell line A549/DDP were 2.38%, 4.01%, 7.43% and 26.43%. In addition, the colony formation density was significantly inhibited with the increase of scutellarin concentration. The concentration of 80 μmol·L-1 was selected to be the reversal concentration, because its maximum rate was <10%; the DDP-resistance significantly decreased in A549/DDP cells after scutellarin and DDP co-treatment. Western blotting results showed that the expression level of c-met significantly decreased in A549/DDP cells after treatment with scutellarin combined with DDP. CONCLUSION Scutellarin combined with DPP can reverse the DDP resistance of A549/DDP cells, inhibit the colony formation and its potential mechanism may be related to the down-regulation of c-met protein expression.
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