BACKGROUND: Chemotherapy-induced nuclear factor kappaB (NFκB) activation is thought to play a key role in acquisition of chemoresistance by cancer cells. We focused on blockade of this activation by using the observation so-called 'desensitization' of NFκB using known NFκB activator, doxycycline. MATERIALS AND METHODS: The human pancreatic cancer cell line PANC-1 was incubated with doxycycline, followed by treatment with tumor necrosis factor (TNF)-α or paclitaxel. NFκB activity and the regulation of NFκB-related genes was analyzed. RESULTS: Doxycycline induced sustained NFκB activation, followed by desensitization to further NFκB activation by TNF-α -or paclitaxel, which was accompanied by decreased expression of TNF receptor p55, p75, and epidermal growth factor receptor. Consistent with these observations, doxycycline-pre-treatment resulted in an augmentation of TNF-α- and paclitaxel-mediated cytotoxicity and apoptosis. CONCLUSION: These data indicate the possible clinical application of desensitization of NFκB to overcome chemoresistance by conventional chemotherapy for pancreatic cancer.
BACKGROUND: Chemotherapy-induced nuclear factor kappaB (NFκB) activation is thought to play a key role in acquisition of chemoresistance by cancer cells. We focused on blockade of this activation by using the observation so-called 'desensitization' of NFκB using known NFκB activator, doxycycline. MATERIALS AND METHODS: The humanpancreatic cancer cell line PANC-1 was incubated with doxycycline, followed by treatment with tumor necrosis factor (TNF)-α or paclitaxel. NFκB activity and the regulation of NFκB-related genes was analyzed. RESULTS:Doxycycline induced sustained NFκB activation, followed by desensitization to further NFκB activation by TNF-α -or paclitaxel, which was accompanied by decreased expression of TNF receptor p55, p75, and epidermal growth factor receptor. Consistent with these observations, doxycycline-pre-treatment resulted in an augmentation of TNF-α- and paclitaxel-mediated cytotoxicity and apoptosis. CONCLUSION: These data indicate the possible clinical application of desensitization of NFκB to overcome chemoresistance by conventional chemotherapy for pancreatic cancer.
Authors: Suparna Qanungo; Joachim D Uys; Yefim Manevich; Anne M Distler; Brooke Shaner; Elizabeth G Hill; John J Mieyal; John J Lemasters; Danyelle M Townsend; Anna-Liisa Nieminen Journal: Biomed Pharmacother Date: 2014-08-28 Impact factor: 6.529
Authors: Ji Ho Kang; Hye Seon Kang; In Kyoung Kim; Hwa Young Lee; Jick Hwan Ha; Chang Dong Yeo; Hyun Hui Kang; Hwa Sik Moon; Sang Haak Lee Journal: Exp Biol Med (Maywood) Date: 2015-02-25