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PSK-mediated NF-κB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1

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-κB) activation. Moreover, the expression of cellular inhibitor of apoptosis protein (cIAP-1), which is transcriptionally regulated by NF-κB 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-κB 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-κB activation pathway. Combination of PSK with a low dose of docetaxel may be a new therapeutic strategy to treat patients with pancreatic cancer.

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Correspondence to Takashi Morisaki.

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Zhang, H., Morisaki, T., Nakahara, C. et al. PSK-mediated NF-κB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1. Oncogene 22, 2088–2096 (2003). https://doi.org/10.1038/sj.onc.1206310

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  • DOI: https://doi.org/10.1038/sj.onc.1206310

Keywords

  • pancreatic cancer
  • docetaxel
  • PSK
  • apoptosis
  • NF-κB

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