Huarong Huang1, Xiao-Xing Cui2, Shaohua Chen3, Susan Goodin4, Yue Liu2, Yan He1, Dongli Li1, Hong Wang2, Jeremiah Van Doren2, Robert S Dipaola4, Allan H Conney5, Xi Zheng6. 1. Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, P.R. China. 2. Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A. 3. Guangdong Provincial People's Hospital, Guangzhou, P.R. China. 4. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A. 5. Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, P.R. China Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A. 6. Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, P.R. China Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A. xizheng@pharmacy.rutgers.edu.
Abstract
BACKGROUND/AIM: Lipitor is a cholesterol-lowering drug and Celebrex is a Cyclooxygenase-2 inhibitor. We investigated the effects of Lipitor and Celebrex on human prostate cancer VCaP cells cultured in vitro and grown as orthotopic xenograft tumors in SCID mice. MATERIALS AND METHODS: Apoptosis was measured by morphological assessment and caspase-3 assay. Nuclear factor-kappa B (NF-κB) activation was determined by luciferase reporter assay. B-cell lymphoma-2 (Bcl2) was measured by western blotting and immunohistochemistry. Orthotopic prostate tumors were monitored by the IVIS imaging system. RESULTS: the combination of Lipitor and Celebrex had stronger effects on the growth and apoptosis of VCaP cells than did either drug alone. The combination more potently inhibited activation of NFκB and expression of Bcl2 than either drug alone. The growth of orthotopic VCaP prostate tumors was strongly inhibited by treatment with the drug combination. CONCLUSION: Administration of Lipitor and Celebrex in combination may be an effective strategy for inhibiting the growth of prostate cancer. Copyright
BACKGROUND/AIM: Lipitor is a cholesterol-lowering drug and Celebrex is a Cyclooxygenase-2 inhibitor. We investigated the effects of Lipitor and Celebrex on humanprostate cancerVCaP cells cultured in vitro and grown as orthotopic xenograft tumors in SCIDmice. MATERIALS AND METHODS: Apoptosis was measured by morphological assessment and caspase-3 assay. Nuclear factor-kappa B (NF-κB) activation was determined by luciferase reporter assay. B-cell lymphoma-2 (Bcl2) was measured by western blotting and immunohistochemistry. Orthotopic prostate tumors were monitored by the IVIS imaging system. RESULTS: the combination of Lipitor and Celebrex had stronger effects on the growth and apoptosis of VCaP cells than did either drug alone. The combination more potently inhibited activation of NFκB and expression of Bcl2 than either drug alone. The growth of orthotopic VCaP prostate tumors was strongly inhibited by treatment with the drug combination. CONCLUSION: Administration of Lipitor and Celebrex in combination may be an effective strategy for inhibiting the growth of prostate cancer. Copyright
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