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.
Anticancer Res. 2014 Jul;34(7):3357-63.
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.
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.
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.
Administration of Lipitor and Celebrex in combination may be an effective strategy for inhibiting the growth of prostate cancer.
背景/目的:立普妥(Lipitor)是一种降胆固醇药物,西乐葆(Celebrex)是一种环氧化酶-2 抑制剂。我们研究了立普妥和西乐葆对体外培养的人前列腺癌 VCaP 细胞和 SCID 小鼠原位移植肿瘤的影响。
通过形态学评估和 caspase-3 测定来检测细胞凋亡。通过荧光素酶报告基因检测来确定核因子-κB(NF-κB)的激活。通过 Western 印迹和免疫组化来检测 B 细胞淋巴瘤-2(Bcl2)。通过 IVIS 成像系统监测原位前列腺肿瘤。
与单独使用任一药物相比,立普妥和西乐葆联合使用对 VCaP 细胞的生长和凋亡有更强的作用。与单独使用任一药物相比,联合用药更能抑制 NFκB 的激活和 Bcl2 的表达。药物联合治疗强烈抑制了原位 VCaP 前列腺肿瘤的生长。
联合使用立普妥和西乐葆可能是抑制前列腺癌生长的有效策略。