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PSK-mediated NF-?B inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1.
- Source :
-
Oncogene . 4/10/2003, Vol. 22 Issue 14, p2088. 9p. - Publication Year :
- 2003
-
Abstract
- Docetaxel, a member of the taxane family, has been shown to induce apoptosis in a variety of cancer cells. However, toxicity at therapeutic doses has precluded the use of docetaxel alone for the management of cancer patients. PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients. Our previous study showed that PSK induced downregulation of several invasion-related factors, suggesting an interaction of PSK with transcriptional factors. In this study, we showed that PSK dose dependently enhanced apoptosis induced by 1?nM of docetaxel in a human pancreatic cancer cell line NOR-P1. Furthermore, PSK inhibited docetaxel-induced nuclear factor kappa B (NF-?B) activation. Moreover, the expression of cellular inhibitor of apoptosis protein (cIAP-1), which is transcriptionally regulated by NF-?B and functions as an antiapoptotic molecule through interrupting the caspase pathway, was also inhibited by treatment with PSK plus docetaxel. As a result, PSK enhanced the docetaxel-induced caspase-3 activation. In addition, treatment by transfection of NF-?B decoy oligodeoxynucleotides (ODNs), but not scramble ones, inhibited the expression of cIAP-1 in NOR-P1 cells and induced a significant increase in docetaxel-induced apoptosis. Our data indicate that PSK suppresses the docetaxel-induced NF-?B activation pathway. Combination of PSK with a low dose of docetaxel may be a new therapeutic strategy to treat patients with pancreatic cancer.Oncogene (2003) 22, 2088-2096. doi:10.1038/sj.onc.1206310 [ABSTRACT FROM AUTHOR]
- Subjects :
- *DOCETAXEL
*APOPTOSIS
*CANCER cells
*POLYSACCHARIDES
*PANCREATIC cancer
Subjects
Details
- Language :
- English
- ISSN :
- 09509232
- Volume :
- 22
- Issue :
- 14
- Database :
- Academic Search Index
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 9482770
- Full Text :
- https://doi.org/10.1038/sj.onc.1206310