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

Oncogene volume 22, pages 2088–2096 (2003)Cite this article

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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References

  • Anai H, Sakaguchi Y, Emi Y, Kohnoe S, Maehara Y and, Sugimachi K . (1991). Anticancer Drugs, 2, 275–278.

  • Aota K, Azuma M, Yamashita T, Tamatani T, Motegi K, Ishimaru N, Hayashi Y and Sato M . (2000). Biochem. Biophys. Res. Commun., 273, 1168–1174.

  • Arlt A, Vorndamm J, Breitenbroich M, Folsch UR, Kalthoff H, Schmidt WE and Schafer H . (2001). Oncogene, 20, 859–868.

  • Bargou RC, Emmerich F, Krappmann D, Bommert K, Mapara MY, Arnold W, Royer HD, Grinstein E, Greiner A, Scheidereit C and Dorken B . (1997). J. Clin. Invest., 100, 2961–2969.

  • Bissery MC, Nohynek G, Sanderink GJ and Lavelle F . (1995). Anticancer Drugs, 6, 339–355.

  • Cascinu S, Gasparini G, Catalano V, Silva RR, Pancera G, Morabito A, Giordani P, Gattuso D and Catalano G . (1999). Ann. Oncol., 10, 1377–1379.

  • Chu ZL, Mckinsey TA, Liu L, Gentry JJ, Malim MH and Ballard DW . (1997). Pro. Natl. Acad. Sci. USA, 94, 10057–10062.

  • Cortes JE and Pazdur R . (1995). J. Clin. Oncol., 13, 2643–2655.

  • Cui X, Imaizumi T, Yoshida H, Tanji K, Matsumiya T and Satoh K . (2000). Biochim. Biophys. Acta, 1524, 178–182.

  • Ebina T and Murata K . (1992). Jpn. J. Cancer Res., 83, 775–782.

  • Fisher M and Yang LX . (2002). Anticancer Res., 22, 1737–1754.

  • Fukushima M . (1996). Semin. Oncol., 23, 369–378.

  • Haldar S, Basu A and Croce CM . (1997). Cancer Res., 57, 229–233.

  • Huang Y, Johnson KR, Norris JS and Fan W . (2000). Cancer Res., 60, 4426–4432.

  • Iino Y, Takai Y, Sugamata N and Morishita Y . (1992). Anticancer Res., 12, 2101–2103.

  • Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y and Ueno K . (1996). Biol. Pharm. Bull., 19, 1518–1520.

  • Iwaguchi T, Shimizu M and Hayashi H . (1989). J. Biochem. Biophys. Methods, 18, 157–166.

  • Kaye SB . (1995). Semin. Oncol., 22, 30–33.

  • Kojima M, Morisaki T, Izuhara K, Uchiyama A, Matsunari Y, Katano M and Tanaka M . (2000). Oncogene, 19, 1225–1231.

  • Kolfschoten GM, Hulscher TM, Duyndam MC, Pinedo HM and Boven E . (2002). Biochem. Pharmacol., 63, 733–743.

  • Lenzi R, Yalcin S, Evans DB and Abbruzzese JL . (2002). Cancer Invest., 20, 464–472.

  • Mori H, Mihara M, Teshima K, Uesugi U, Xu Q, Sakamoto O and Koda A . (1987). Int. J. Immunopharmacol., 9, 881–892.

  • Nicoletti I, Migliorati G, Pagliacci MC, Grignani F and Riccardi C . (1991). J. Immunol. Methods, 139, 271–279.

  • Okada S, Sakata Y, Matsuno S, Kurihara M, Sasaki Y, Ohashi Y and Taguchi T . (1999). Br. J. Cancer, 80, 438–443.

  • Rougier P, Adenis A, Ducreux M, de Forni M, Bonneterre J, Dembak M, Clouet P, Lebecq A, Baille P, Lefresne-Soulas F, Blanc C and Armand JP . (2000). Eur. J. Cancer, 36, 1016–1025.

  • Rowinsky EK . (1997). Annu. Rev. Med., 48, 353–374.

  • Roy N, Deveraux QL, Takahashi R, Salvesen GS and Reed JC . (1997). EMBO J., 16, 6914–6925.

  • Sato N, Mizumoto K, Beppu K, Maehara N, Kusumoto M, Nabae T, Morisaki T, Katano N and Tanaka M . (2000). Cancer Lett., 155, 153–161.

  • Shibata M, Nezu T, Kanou H, Nagata Y, Kimura T, Takekawa M, Anclo K and Fukuzawa M . (2002). Cancer Invest., 20, 166–173.

  • Spencer W, Kwon H, Crepieux P, Leclerc N, Lin R and Hiscott J . (1999). Oncogene, 18, 495–505.

  • Stathopoulos GP, Mavroudis D, Tsavaris N, Kouroussis C, Aravantinos G, Agelaki S, Kakolyris S, Rigatos SK, Karabekios S and Georgoulias V . (2000). Ann. Oncol., 12, 101–103.

  • Takahashi Y and Mai M . (2001). Gan To Kagaku Ryoho, 28, 531–534.

  • Tsukagoshi S, Hashimoto Y, Fujii G, Kobayashi H, Nomoto K and Orita K . (1984). Cancer Treat. Rev., 11, 131–155.

  • Vos IH, Govers R, Grone HJ, Kleij L, Schurink M, De Weger RA, Goldschmeding R and Rabelink TJ . (2000). FASEB. J., 14, 815–822.

  • Wang CY, Mayo MW, Korneluk RG, Goeddel DV and Baldwin Jr AS . (1998). Science, 281, 1680–1683.

  • Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR and Chiao PJ . (1999). Clin. Cancer Res., 5, 119–127.

  • Wright ME, Han DK and Hockenbery DM . (2000). FEBS Lett., 481, 13–18.

  • Zhang H, Morisaki T, Matsunaga H, Sato N, Uchiyama A, Hashizume K, Nagumo F, Tadano J and Katano M . (2000). Clin. Exp. Metast., 18, 343–352.

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Authors and Affiliations

  1. Department of Hospital Clinical Laboratory, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Hao Zhang, Fumio Nagumo & Jutaro Tadano

  2. Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Hao Zhang, Takashi Morisaki, Chihiro Nakahara & Mitsuo Katano

  3. Department of Hospital Pharmacy, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Hisashi Matsunaga

  4. Department of Clinical Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Noshiro Sato

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  1. Hao Zhang
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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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