Synergy of gemcitabine and lidamycin associated with NF-κB downregulation in pancreatic carcinoma cells
被引:10
作者:
Chen, Jing
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机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R China
N China Coal Med Coll, Tangshan 063000, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Chen, Jing
[1
,2
,3
]
Wu, Shu-ying
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机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Wu, Shu-ying
[1
,2
]
Ou-Yang, Zhi-gang
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机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Ou-Yang, Zhi-gang
[1
,2
]
Zhen, Yong-su
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机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Zhen, Yong-su
[1
,2
]
机构:
[1] Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
[2] Peking Union Med Coll, Beijing 100050, Peoples R China
[3] N China Coal Med Coll, Tangshan 063000, Peoples R China
lidamycin;
gemcitabine;
pancreatic cancer;
K-ras;
NF-kappa B;
drug therapy;
combination;
D O I:
10.1111/j.1745-7254.2008.00774.x
中图分类号:
O6 [化学];
学科分类号:
0703 ;
摘要:
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-kappa B, 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-kappa B, 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-kappa B downregulation.
机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Huang, Yun-Hong
;
Shang, Bo-Yang
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机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Shang, Bo-Yang
;
Zhen, Yong-Su
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Huang, Yun-Hong
;
Shang, Bo-Yang
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Shang, Bo-Yang
;
Zhen, Yong-Su
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China
Peking Union Med Coll, Beijing 100050, Peoples R ChinaChinese Acad Med Sci, Inst Med Biotechnol, Beijing 100050, Peoples R China