Zheng Xi, Cui Xiao-Xing, Avila Gina E, Huang Mou-Tuan, Liu Yue, Patel Jagruti, Kong Ah Ng Tony, Paulino Raphael, Shih Weichung Joe, Lin Yong, Rabson Arnold B, Reddy Bandaru S, Conney Allan H
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5480-7. doi: 10.1158/1078-0432.CCR-07-0242.
To investigate the effects and mechanisms of atorvastatin and celecoxib administered individually or in combination on human prostate cancer PC-3 cells cultured in vitro or grown as xenograft tumors in immunodeficient mice.
Human prostate cancer PC-3 cells in culture were treated with atorvastatin and celecoxib alone or in combination. Severe combined immunodeficient (SCID) mice were injected s.c. with PC-3 cells. The mice received daily i.p injections starting 2 days before tumor cell inoculation and continuing during the course of treatment with atorvastatin (10 microg/g body weight/d), celecoxib (10 microg/g/d), a combination of atorvastatin (10 microg/g/d) and celecoxib (10 microg/g/d), or a combination of atorvastatin (5 microg/g/d) and celecoxib (5 microg/g/d).
Atorvastatin in combination with celecoxib had stronger effects on growth inhibition and apoptosis of PC-3 cells than either agent used individually. Atorvastatin and celecoxib in combination also had a stronger inhibitory effect on activation of nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 in PC-3 cells than either agent alone. Treatment of SCID mice with combinations of atorvastatin and celecoxib more effectively inhibited the formation and growth of PC-3 tumors in the mice than either agent administered alone.
A combination of atorvastatin and celecoxib had a more potent inhibitory effect on the growth of PC-3 cells cultured in vitro or grown in SCID mice than either agent alone. A combination of atorvastatin and celecoxib may be an effective strategy for the prevention of prostate cancer.
研究阿托伐他汀和塞来昔布单独或联合应用对体外培养的人前列腺癌PC-3细胞或在免疫缺陷小鼠体内生长的异种移植瘤的影响及作用机制。
体外培养的人前列腺癌PC-3细胞分别用阿托伐他汀和塞来昔布单独或联合处理。将严重联合免疫缺陷（SCID）小鼠皮下注射PC-3细胞。从肿瘤细胞接种前2天开始，小鼠每天腹腔注射阿托伐他汀（10微克/克体重/天）、塞来昔布（10微克/克/天）、阿托伐他汀（10微克/克/天）与塞来昔布（10微克/克/天）的组合或阿托伐他汀（5微克/克/天）与塞来昔布（5微克/克/天）的组合，并持续至治疗过程结束。
阿托伐他汀与塞来昔布联合应用对PC-3细胞生长抑制和凋亡的作用比单独使用任何一种药物都更强。阿托伐他汀和塞来昔布联合应用对PC-3细胞中核因子-κB和细胞外信号调节激酶1/2激活的抑制作用也比单独使用任何一种药物更强。用阿托伐他汀和塞来昔布联合治疗SCID小鼠比单独使用任何一种药物更有效地抑制了小鼠体内PC-3肿瘤的形成和生长。
阿托伐他汀和塞来昔布联合应用对体外培养的或在SCID小鼠体内生长的PC-3细胞生长的抑制作用比单独使用任何一种药物都更强。阿托伐他汀和塞来昔布联合应用可能是预防前列腺癌的有效策略。
