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Tamoxifen

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Catalog No.
B5965
TGF-β调节和PKC抑制效应
组合的产品项目
规格价格库存 数量
1g
¥ 650.00
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5g
¥ 2,100.00
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10g
¥ 3,600.00
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Background

IC50: 5.5–10 μM

Transforming growth factor-β (TGF-β) is a growth factor which is capable of inhibiting prostate cell growth in vitro, and has apparent prostate cell growth regulatory roles in vivo. A second element of potential importance in regulating the growth of prostate cancer cells is the serine/threonine kinase, protein kinase C (PKC). PKC is a signaling enzyme of known importance in regulating the growth and/or differentiation of a variety of cell types; inhibition of its kinase activity is associated with loss of regulatory function. Tamoxifen is a drug known to have TGF-β modulatory and PKC inhibitory effects.

In vitro: IC50s for growth inhibition ranged from 5.5–10 μM, and were not affected by estrogen. Tamoxifen-mediated growth inhibition was not associated with induction of TGF-β. However, tamoxifen treatment was associated with inhibition of PKC, which was followed by induction of p21waf1/cip1, Rb dephosphorylation, and G1/S phase cell cycle arrest [1].

In vivo: The tumor cell kinetics of MCF-7 human breast carcinoma xenografts grown in nude mice can be significantly altered by hormonal manipu lation. Tamoxifen treatment or E2 deprivation resulted in an approximate doubling of the Tpol and an approximately 40% reduction in labeling index as compared to E2-stimulated tumors. An increase in cell loss rate was calculated for both tamoxifen treatment and E2 deprivation [2].

Clinical trial: Tamoxifen reduces the risk of recurrence and death from breast cancer when given as adjuvant therapy, and it provides effective palliation for metastatic breast cancer. Its use is therefore indicated for both premenopausal and postmenopausal women having estrogen-receptor–positive invasive breast cancer [3].

References:
[1] Rohlff C, Blagosklonny MV, Kyle E, Kesari A, Kim IY, Zelner DJ, Hakim F, Trepel J, Bergan RC.  Prostate cancer cell growth inhibition by tamoxifen is associated with inhibition of protein kinase C and induction of p21(waf1/cip1). Prostate. 1998 Sep 15;37(1):51-9.
[2] Jann N.  Sarkaria, David F. C. Gibson, V. Craig Jordan, John F. Fowler, Mary J. Lindstrom, and
R.  Timothy Mulcahy. Tamoxifen-induced Increase in the Potential Doubling Time of MCF-7 Xenografts as Determined by Bromodeoxyuridine Labeling and Flow Cytometry. CANCER RESEARCH 5.1. 4413-1417, September 15, 1993.
[3] Osborne CK.  Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998 Nov 26;339(22):1609-18.

文献引用

1. Ungerleider NA, Rao SG, et al. "Breast cancer survival predicted by TP53 mutation status differs markedly depending on treatment." Breast Cancer Res. 2018 Oct 1;20(1):115. PMID:30285883

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt371.51
Cas No.10540-29-1
FormulaC26H29NO
Solubility≥18.6mg/mL in DMSO
Chemical Name2-[4-[(1Z)-1,2-diphenyl-1-buten-1-yl]phenoxy]-N,N-dimethyl-ethanamine
SDFDownload SDF
Canonical SMILESCC/C(C1=CC=CC=C1)=C(C2=CC=C(OCCN(C)C)C=C2)\C3=CC=CC=C3
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

PC3和PC3-M前列腺癌细胞,DU-145细胞

溶解方法

该化合物在DMSO中的溶解度大于18.6 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

10 μM,3 days

应用

在PC3-M细胞中,Tamoxifen治疗3天以剂量依赖性方式抑制细胞生长。Tamoxifen(10 μM)抑制蛋白激酶C活性。Tamoxifen和TGF-β增加PC3-M细胞中胸腺嘧啶核苷的摄取。Tamoxifen治疗后12小时,细胞溶质Rb蛋白持续下降,持续至少24小时。在细胞核中,Tamoxifen治疗后12-24小时,磷酸化形式的Rb消失。

动物实验 [2]:

动物模型

MCF-7异种移植的卵巢切除裸鼠

给药剂量

21天

应用

TAM治疗减缓肿瘤生长,肿瘤倍增时间为12天,Tpot显著增加至6.6天,治疗后23天%LI下降到8%。TAM治疗显著降低MCF-7异种移植物中的肿瘤细胞增殖。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Rohlff C, Blagosklonny M V, Kyle E, et al. Prostate cancer cell growth inhibition by tamoxifen is associated with inhibition of protein kinase C and induction of p21waf1/cip1[J]. The Prostate, 1998, 37(1): 51-59.

[2]. Sarkaria J N, Gibson D F C, Jordan V C, et al. Tamoxifen-induced increase in the potential doubling time of MCF-7 xenografts as determined by bromodeoxyuridine labeling and flow cytometry[J]. Cancer research, 1993, 53(18): 4413-4417.

质量控制

化学结构

Tamoxifen

相关生物数据

Tamoxifen