Abstract
Aim:
To investigate the effects on human pancreatic cancer PANC-1 and SW1990 cells using a combination of lidamycin (LDM) and gemcitabine.
Methods:
A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the growth inhibition of drugs in PANC-1 and SW1990 cells. The effects on apoptosis were measured by terminal uridine deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometry combined with fluorescein-isothiocyanate-Annexin V/propidium iodide staining. The activity of caspase-3 was measured with a special assay kit. The mitochondrial membrane potential was determined by confocal microscopy analyses. The level of mRNA encoding K-ras in the cells was determined by RT-PCR analysis. The expression of K-ras, NF-κB, and Bcl-2 was detected by Western blotting analysis.
Results:
There was a significant reduction in proliferation in the pancreatic cancer cell lines treated with a combination of gemcitabine and LDM. The overall growth inhibition directly correlated with apoptotic cell death. LDM potentiated the gemcitabine-induced cell killing by reducing mitochondrial membrane potential and increasing the caspase-3 activity. Notably, the K-ras mRNA level was significantly reduced with the combination of gemcitabine and LDM. The results for K-ras, NF-κB, and Bcl-2 proteins also showed downregulation in the combination group relative to the single-agent treatment and the untreated control.
Conclusion:
LDM can potentiate the growth inhibition induced by gemcitabine in human pancreatic cancer cells, and the synergy may be associated with NF-κB downregulation.
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This work was supported by The National High Technology Research and Development Program of China (No 2004AA2Z3950) and a grant from the National Natural Science Foundation of China (No 30400597).
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Chen, J., Wu, Sy., Ou-yang, Zg. et al. Synergy of gemcitabine and lidamycin associated with NF-κB downregulation in pancreatic carcinoma cells. Acta Pharmacol Sin 29, 614–619 (2008). https://doi.org/10.1111/j.1745-7254.2008.00774.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00774.x
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