Abstract
Drug resistance is one characteristic of hepatocellular carcinoma (HCC) and can affect the prognosis of patients directly. To explore drug resistance well, we established an oxaliplatin (OXA)-resistant cell line Bel-7402/OXA by exposure to gradually increased concentration of OXA. Some biological characters, such as proliferation, migration, and invasion, were studied. Drug sensitivity and the mechanisms of drug resistance were also investigated. We found that the resistant index of Bel-7402/OXA was 8.3. In comparison with Bel-7402, the percentages of cells in S and G2/M phase were increased. The nature apoptosis rate and drug-after apoptosis rate were all decreased in Bel-7402/OXA, as compared to Bel-7402. Bel-7402/OXA acquired increased migration and invasion ability with epithelial–mesenchymal transition (EMT) phenotype. Knockdown of EMT transcription factor Snail could reverse EMT and sensitized Bel-7402/OXA cells to OXA. EMT was one mechanism of drug resistance and may be a novel target of treatment for drug resistance.
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Acknowledgments
This study was supported by the grants from the National Nature Science Foundation of China (No. 30770971, 81172470, 81070362, and 81372629).
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The manuscript has been performed with the approval of the institutional Ethics Committees of Xiangya Hospital, Central South University.
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Supplementary Table S1
The types, dilutions and sources of antibodies used for the Western blot analysis. (DOC 46 kb)
Figure S1
Downregulation of Snail expression by siRNAs in Bel-7402/OXA cells. Western blot (a) and qRT-PCR (b) demonstrated that siRNA 2 had the highest inhibition efficiency of 71.7% in the three candidate sequences. (GIF 10 kb)
Figure S2
Regulation of EMT transcription factors effected OXA resistance. a Cell viability of Bel-7402/OXA after Slug knockdown was measured by CCK-8 assay (p < 0.001). b Cell viability of Bel-7402/OXA after Twist knockdown was measured by CCK-8 assay (p < 0.05). (GIF 29 kb)
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Ma, J., Zeng, S., Zhang, Y. et al. Epithelial–mesenchymal transition plays a critical role in drug resistance of hepatocellular carcinoma cells to oxaliplatin. Tumor Biol. 37, 6177–6184 (2016). https://doi.org/10.1007/s13277-015-4458-z
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DOI: https://doi.org/10.1007/s13277-015-4458-z