Effect of a vitamin D(3) derivative (B3CD) with postulated anti-cancer activity in an ovarian cancer animal model.
Effect of a vitamin D(3) derivative (B3CD) with postulated anti-cancer activity in an ovarian cancer animal model.
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DOI：
10.1007/s10637-009-9284-y
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发表时间：
2010-10
影响因子：
3.4
通讯作者：
Brard, Laurent
中科院分区：
文献类型：
--
作者：
Lange, Thilo S.;Stuckey, Ashley R.;Robison, Katina;Kim, Kyu Kwang;Singh, Rakesh K.;Raker, Christina A.;Brard, Laurent
本研究的目的是利用小鼠卵巢癌异种移植模型，在体内验证钙二醇衍生物B3CD作为潜在抗癌药物的假设。此外，还分析了B3CD对人卵巢癌铂耐药细胞系与对照细胞系的体外活性和增殖的选择性。B3CD显示了针对一组卵巢和其他癌细胞系、内皮细胞和对照细胞的细胞系特异性细胞毒作用。BrdU掺入分析显示，亚细胞毒浓度的B3CD对SKOV-3卵巢癌细胞的增殖抑制作用强于原代成纤维细胞。0.5μM的B3CD处理后，SKOV-3细胞染色质高度浓缩，核碎裂，而原代成纤维细胞则未见。低浓度(≤0.5μM)的B3CD诱导SKOV-3细胞死亡是通过p38MAPK信号通路介导的：B3CD诱导SKOV-3细胞p38MAPK表达和激活，抑制p38信号转导拮抗B3CD诱导的细胞死亡。卵巢癌细胞动物模型(人SKOV-3细胞来源的裸鼠移植瘤)显示，少数B3CD治疗的小鼠肿瘤生长加速，而大多数B3CD治疗的小鼠肿瘤生长延迟或肿瘤完全消退。B3CD在体内外均具有抗卵巢癌的作用。我们建议进一步开发维生素D3的非钙化溴乙酰氧基衍生物作为潜在的抗癌治疗药物。
The objective of the present study was to test the hypothesis that Calcidiol derivative B3CD qualifies as a potential anti-cancer drug in vivo employing an ovarian cancer xenograft model in mice. In addition, the selectivity of B3CD on viability and proliferation of platinum-resistant human ovarian cancer cell lines in comparison to control cell lines was analyzed in vitro. B3CD displayed cell line-specific cytotoxicity screened against a panel of ovarian and other carcinoma cell lines, endothelial and control cells. B3CD, at sub-cytotoxic concentrations, revealed stronger effects on the proliferation of SKOV-3 ovarian cancer cells vs. primary fibroblasts as determined by BrdU incorporation analysis. Treatment with B3CD at 0.5 μM resulted in highly condensed chromatin and fragmented nuclei in SKOV-3 cells but not in primary fibroblasts. B3CD induced cell death at low drug concentrations (≤0.5 μM) in SKOV-3 ovarian cancer cells is mediated by the p38 MAPK signaling pathway: B3CD induced p38 MAPK expression and activation in SKOV-3 cells and inhibition of p38 signaling counteracted B3CD induced cell death in vitro. An ovarian cancer cell animal model (human SKOV-3 cell derived xenografts in nude mice) revealed that tumor growth in few B3CD treated mice accelerated while the majority of B3CD treated mice displayed delayed tumor growth or full tumor regression. B3CD possesses anti-ovarian cancer properties in vitro and in vivo. We propose the further development of non-calcemic bromoacetoxy derivatives of vitamin D3 as potential anti-cancer therapeutics.
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影响因子：
5.7
作者：
Benedetti, Valentina;Perego, Paola;Zunino, Franco
通讯作者：
Zunino, Franco
DOI：
10.1016/j.jsbmb.2006.12.042
发表时间：
2007-03-01
影响因子：
4.1
作者：
Chung, Ivy;Yu, Wei-Dong;Trump, Donald L.
通讯作者：
Trump, Donald L.
影响因子：
3.7
作者：
Lange TS;Kim KK;Singh RK;Strongin RM;McCourt CK;Brard L
通讯作者：
Brard L
DOI：
10.1111/j.1048-891x.2004.014507.x
发表时间：
2004-09-01
影响因子：
4.8
作者：
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通讯作者：
Rustin, GJS
影响因子：
11.2
作者：
Chauhan, Subhash C.;Vannatta, Kelley;Jaggi, Meena
通讯作者：
Jaggi, Meena