Inhibition of NF-kappaB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells.
Inhibition of NF-kappaB by (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY11-7082; BAY) is associated with enhanced 12-O-tetradecanoylphorbol-13-acetate-induced growth suppression and apoptosis in human prostate cancer PC-3 cells.
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发表时间：
2008
影响因子：
5.2
通讯作者：
Xi Zheng;R. Chang;X. Cui;Gina E. Avila;Mou-tuan Huang;Yue Liu;A. Kong;A. Rabson;A. Conney
中科院分区：
文献类型：
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作者：
Xi Zheng;R. Chang;X. Cui;Gina E. Avila;Mou-tuan Huang;Yue Liu;A. Kong;A. Rabson;A. Conney
研究了12-O-十四酰基佛波醇-13-乙酸酯（TPA）单独或与NF-κ B抑制剂（E）3-[（4-甲基苯基）-磺酰基]-2-丙烯腈（BAY 11-7082; BAY）组合对体外培养或在免疫缺陷小鼠中生长的人前列腺癌PC-3细胞的生长和凋亡的影响。TPA（0.2-10 ng/ml）处理PC-3细胞96 h，可引起细胞生长抑制和凋亡，且呈浓度依赖性。BAY抑制PC-3细胞中NF-κ B活性，并增强TPA诱导的PC-3细胞生长抑制和凋亡。在动物研究中，用基质胶中的PC-3细胞皮下注射NCr免疫缺陷小鼠。具有良好建立的肿瘤的小鼠每天接受TPA（100 ng/g体重/天）、BAY（4 μ g/g/天）或TPA（100 ng/g/天）和BAY（4 μ g/g/天）的组合的腹膜内注射，持续36天。在所有溶剂处理的对照小鼠中均发生肿瘤生长。治疗36天后，对照组中肿瘤消退的动物百分比为0%，TPA组为40%，BAY组为50%，TPA + BAY组为100%。机制研究表明，TPA或TPA + BAY治疗小鼠肿瘤的增殖减少，凋亡增加。我们的研究结果表明，NF-κ B活性的抑制与增强TPA诱导的PC-3细胞生长抑制和凋亡有关。通过合适的药理学抑制剂抑制NF-κ B活性可能是提高TPA在前列腺癌中的治疗效果的有效策略。
The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) alone or in combination with an NF-kappaB inhibitor, (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY 11-7082; BAY), on the growth and apoptosis of human prostate cancer PC-3 cells cultured in vitro or grown in immunodeficient mice were studied. Treatment of cultured PC-3 cells with TPA (0.2-10 ng/ml) for 96 h resulted in growth inhibition and apoptosis in a concentration-dependent manner. BAY inhibited NF-kappaB activity in PC-3 cells as determined by a luciferase reporter assay and enhanced TPA-induced growth inhibition and apoptosis in cultured PC-3 cells. In animal studies, NCr immunodeficient mice were injected subcutaneously with PC-3 cells in Matrigel. Mice with well-established tumors received daily i.p. injections with TPA (100 ng/g body weight/day), BAY (4 microg/g/day), or a combination of TPA (100 ng/g/day) and BAY (4 microg/g/day) for 36 days. Tumor growth occurred in all of the vehicle-treated control mice. The percent of animals with some tumor regression after 36 days of treatment was 0% for the control group, 40% for the TPA group, 50% for the BAY group and 100% for the TPA + BAY group. Mechanistic studies indicated that treatment of the mice with TPA or TPA + BAY decreased proliferation and increased apoptosis in the tumors. Results from our studies indicate that inhibition of NF-kappaB activity is associated with enhanced TPA-induced growth inhibition and apoptosis in PC-3 cells. Inhibition of NF-kappaB activity by suitable pharmacological inhibitors may be an effective strategy for improving the therapeutic efficacy of TPA in prostate cancer.