Ping Fang and Xin Zhang are the first authors and contributed equally to the work.
Reversal Effect of Melanoma Differentiation Associated Gene-7/Interleukin-24 on Multidrug Resistance in Human Hepatocellular Carcinoma Cells
Article first published online: 16 AUG 2012
Copyright © 2012 Wiley Periodicals, Inc.
The Anatomical Record
Volume 295, Issue 10, pages 1639–1646, October 2012
How to Cite
Fang, P., Zhang, X., Gao, Y., Ding, C.-R., Cui, F. and Jiao, S.-C. (2012), Reversal Effect of Melanoma Differentiation Associated Gene-7/Interleukin-24 on Multidrug Resistance in Human Hepatocellular Carcinoma Cells. Anat Rec, 295: 1639–1646. doi: 10.1002/ar.22551
- Issue published online: 12 SEP 2012
- Article first published online: 16 AUG 2012
- Manuscript Accepted: 20 JUL 2012
- Manuscript Received: 20 NOV 2011
- drug accumulation and efflux;
- hepatocellular carcinoma;
- multidrug resistance;
- melanoma differentiation associated gene-7/interleukin-24
Multidrug resistance is the main cause for failure of chemotherapy. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) has been implicated in the inhibition of human tumor cell proliferation. However, the reversing effect of mda-7/IL-24 on multidrug resistance of human hepatocellular carcinoma (HCC) is not fully clear. In this study, we investigated the effects of overexpression of the mda-7/IL-24 gene in human HCC. We established mda-7/IL-24 overexpressing BEL-7402/5-fluorouracil (5-FU) cell lines and their drug sensitivity to 5-FU and doxorubicin (DOX) which were investigated by MTT. Furthermore, we investigated the apoptotic rate and the intracellular accumulation of Rhodamine-123 and DOX by flow cytometry. We also studied the expression of multidrug resistance gene 1 (MDR1), lung resistance-related protein (LRP), and multidrug resistance-related protein 1 (MRP1) by real-time polymerase chain reaction and Western blotting. Transcriptional activation of AP-1 and NF-κB was determined by luciferase reporter assay. The drug sensitivity of 5-FU or DOX, the apoptotic rate, and the intracellular accumulation of Rhodamine-123 and DOX were increased, while the mRNA and protein expression levels of MDR1, LRP, and MRP1 were reduced. The transcriptional activation of AP-1 and NF-κB was suppressed in mda-7/IL-24 overexpressing BEL-7402/5-FU cells. Our results demonstrated that mda-7/IL-24 could restore the drug sensitivity through the downregulation of MDR1, MRP1, and LRP expression, as well as the transcriptional activation of AP-1 and NF-κB and effectively reverse MDR. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.