Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo.
Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ of the breast in a human xenograft model and on breast and ovarian cancer cell growth in vitro and in vivo.
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在人异种移植模型以及乳腺癌和卵巢癌细胞的体外和体内，Farnesyl转移酶抑制剂（R115777）对导管癌的原位导管癌的影响。
DOI：
10.1186/bcr1395
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发表时间：
2006
影响因子：
7.4
通讯作者：
Bundred, NJ
中科院分区：
文献类型：
--
作者：
Wärnberg, F;White, D;Anderson, E;Knox, F;Clarke, RB;Morris, J;Bundred, NJ
ras通路对细胞生长和增殖至关重要。研究了一种法尼基转移酶抑制剂R115777在表达不同水平生长因子受体和不同ras状态的癌细胞中的作用。对肿瘤移植和人乳腺导管原位癌（DCIS）在异种移植小鼠模型中的影响也进行了测试。体外建立使细胞数量减少50%所需的浓度（50%抑制浓度）（MDA-MB231、MCF-7、MCF-7/HER2-18、BT-474、SK-BR3和SKOV3）。将人DCIS植入裸鼠体内，或在单独的实验中，将培养的细胞注射（MDA-MB231、MCF-7/HER2-18、SKOV3），使其形成肿瘤。免疫组化法检测异种移植物和肿瘤细胞的增殖和凋亡。50%的抑制浓度变化了100倍，从SKBR3的39 μmol/l（±26 nmol/l）到MDA-MB231的5.9 μmol/l（±0.8 μmol/l）。在MCF-7/HER2-18和SKOV3细胞中，肿瘤生长抑制水平分别约为85%和40%。细胞周转指数（CTI；增殖/凋亡）显著降低。活化的k-ras对MDA-MB 231无抑制作用。经治疗的DCIS异种移植物增殖减少，细胞凋亡增加。治疗1和2周后，对照组的CTI比值分别为1.99和1.50，异种移植物组的CTI比值分别为0.85 （P = 0.005）和0.75 （P = 0.08）。用法尼基转移酶抑制剂治疗降低了体外细胞生长和体内细胞肿瘤生长。DCIS治疗导致CTI降低。R115777是一种很有前景的乳腺癌治疗方法，但其疗效与生长因子受体和ras状态之间的关系尚待确定。
The ras pathway is essential for cell growth and proliferation. The effects of R115777, a farnesyl transferase inhibitor, were investigated in cancer cell lines expressing varying levels of growth factor receptors and with differing ras status. Effects on tumour xenografts and human ductal carcinoma in situ (DCIS) of the breast in a xenograft mouse model were also tested. In vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3 and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments, cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to form tumours. Proliferation and apoptosis were determined by immunohistochemistry in xenografts and cell tumours. The 50% inhibitory concentrations varied a hundred-fold, from 39 nmol/l (± 26 nmol/l) for SKBR3 to 5.9 μmol/l(± 0.8 μmol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of tumour growth inhibition were approximately 85% and 40%, respectively. There was a significant decrease in the cell turnover index (CTI; proliferation/apoptosis). In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS xenografts proliferation decreased and apoptosis increased. The CTI ratio between the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts. Treatment with the farnesyl transferase inhibitor reduced cell growth in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced CTI. R115777 is a promising treatment for breast cancer but the relation between effect and growth factor receptor and ras status has to be established.
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影响因子：
45.3
作者：
Johnston, SRD;Hickish, T;Howes, A
通讯作者：
Howes, A
影响因子：
2.5
作者：
Malaney, S;Daly, RJ
通讯作者：
Daly, RJ
DOI：
10.1073/pnas.93.9.4454
发表时间：
1996-04-30
影响因子：
11.1
作者：
James, G;Goldstein, JL;Brown, MS
通讯作者：
Brown, MS
影响因子：
3.8
作者：
Moasser, MM;Rosen, N
通讯作者：
Rosen, N
影响因子：
2.4
作者：
Dy, GK;Adjei, AA
通讯作者：
Adjei, AA