Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line.
Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line.
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DOI：
10.1186/1479-5876-6-43
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发表时间：
2008-08-08
影响因子：
7.4
通讯作者：
Zoli, Wainer
中科院分区：
文献类型：
--
作者：
Fabbri, Francesco;Brigliadori, Giovanni;Carloni, Silvia;Ulivi, Paola;Vannini, Ivan;Tesei, Anna;Silvestrini, Rosella;Amadori, Dino;Zoli, Wainer
在前列腺癌中，识别能够减少肿瘤细胞数量并迅速消除潜在的激素抵抗细胞的药物组合将是这种疾病治疗方面的重大突破。这项研究是在激素敏感的前列腺癌细胞系(LNCaP)上进行的，该细胞系生长在正常或激素剥离的木炭(C.S.)中。5~6成熟。SRB法检测细胞存活率，Annexin-V/TUNEL法检测细胞凋亡率。免疫印迹法检测活化的caspase-3、p21、pMEK和MCL-1的表达水平。唑来膦酸[10 0μM]和多西紫杉醇[0.0 1μM]同时作用1h，再与唑来膦酸共同作用72、96或12 0h，细胞存活率显著下降(R指数=5.1)。这种细胞毒作用与LNCaP和C.S中高度诱导细胞凋亡有关。LNCaP细胞。细胞凋亡的诱导与pMEK和Mcl-1表达的减少是平行的。唑来膦酸与多西紫杉醇联用对正常或无激素培养的LNCaP细胞有非常显著的协同作用，其主要分子机制与细胞凋亡及pMEK和Mcl-1表达降低有关。这个实验得出的时间表似乎阻止了激素抵抗细胞克隆的选择和放大，因此可能与标准的雄激素剥夺疗法一起用于激素敏感型前列腺癌的治疗。
In prostate cancer, the identification of drug combinations that could reduce the tumor cell population and rapidly eradicate hormone-resistant cells potentially present would be a remarkable breakthrough in the treatment of this disease. The study was performed on a hormone-sensitive prostate cancer cell line (LNCaP) grown in normal or hormone-deprived charcoal-stripped (c.s.) medium. Cell viability and apoptosis were assessed by SRB assay and Annexin-V/TUNEL assays, respectively. Activated caspase-3, p21, pMEK and MCL-1 expression levels were detected by western blotting. The simultaneous exposure of zoledronic acid [100 μM] and docetaxel [0.01 μM] for 1 h followed by treatment with zoledronic acid for 72, 96 or 120 h produced a high synergistic interaction (R index = 5.1) with a strong decrease in cell viability. This cytotoxic effect was associated with a high induction of apoptosis in both LNCaP and in c.s. LNCaP cells. The induction of apoptosis was paralleled by a decrease in pMEK and Mcl-1 expression. The zoledronic acid-docetaxel combination produced a highly significant synergistic effect on the LNCaP cell line grown in normal or hormone-deprived medium, the principal molecular mechanisms involved being apoptosis and decreased pMEK and Mcl-1 expression. This experimentally derived schedule would seem to prevent the selection and amplification of hormone-resistant cell clones and could thus be potentially used alongside standard androgen deprivation therapy in the management of hormone-sensitive prostate carcinoma.
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涉及多西他赛的细胞凋亡的顺序事件，一种微管裂化剂：一项细胞仪研究。
影响因子：
--
作者：
Fabbri, F;Carloni, S;Brigliadori, G;Zoli, W;Lapalombella, R;Marini, M
通讯作者：
Marini, M
DOI：
10.1093/jnci/83.11.757
发表时间：
1991-06-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
MONKS, A;SCUDIERO, D;BOYD, M
通讯作者：
BOYD, M
影响因子：
7.2
作者：
Fabbri, F;Brigliadori, G;Zoli, W
通讯作者：
Zoli, W
影响因子：
3.1
作者：
Morgan, Claire;Lewis, Paul D.;Leonard, Robert C. F.
通讯作者：
Leonard, Robert C. F.
影响因子：
3.8
作者：
Brunsvig, Paal Fr;Andersen, Anders;Olsen, Harald
通讯作者：
Olsen, Harald