Doxorubicin (Hydroxydaunorubicin) hydrochloride 是一种具有细胞毒性的蒽环类抗生素，是一种抗癌化疗试剂。Doxorubicin hydrochloride 是一种有效的人类DNA topoisomerase I和topoisomerase II抑制剂，IC50分别为 0.8 μM 和 2.67 μM。Doxorubicin hydrochloride 可降低 AMPK 及其下游靶蛋白乙酰辅酶 A 羧化酶的磷酸化。还可诱导凋亡 (apoptosis) 和自噬。
| 生物活性 | Doxorubicin (Hydroxydaunorubicin) hydrochloride, a cytotoxic anthracyclineantibiotic, is an anti-cancer chemotherapy agent. Doxorubicin hydrochloride is a potent humanDNAtopoisomeraseIandtopoisomeraseIIinhibitor withIC50s of 0.8 μM and 2.67 μM, respectively. Doxorubicin hydrochloride reduces basal phosphorylation ofAMPKand its downstream targetacetyl-CoA carboxylase. Doxorubicin hydrochloride inducesapoptosisandautophagy[1][2][3]. |
| IC50& Target[1][2][3] | Topoisomerase I 0.8 μM (IC50) | Topoisomerase II 2.67 μM (IC50) | Daunorubicins/Doxorubicins | HIV-1 |
|
体外研究
(In Vitro) | Doxorubicin hydrochloride (1-8 μM; 24 and 48 hours) decreases the viability of MCF-10F, MCF-7 and MDA-MB-231 cells in a time- and dose-dependent manner[4].
Doxorubicin hydrochloride (1 μM; 3 and 24 hours) results in Hct-116 human colon carcinoma cells reduction in G0/G1 phase and accumulation in G2 phase[5].
Doxorubicin hydrochloride (1 μM for MCF-10F and MDA-MB-231 cells, 4 μM for MCF-7 cells; 48 hours) induces apoptosis by upregulating Bax, caspase-8 and caspase-3 and downregulation of Bcl-2 protein expression[4].
Cell Viability Assay[4] | Cell Line: | Breast cancer cell lines MCF-10F, MCF-7 and MDA-MB-231 | | Concentration: | 0, 1, 2, 4 and 8 μM | | Incubation Time: | 24 and 48 hours | | Result: | IC50was 1 μM for both MCF-10F and MDA-MB-231 cell lines.
IC50was 4 μM for MCF-7 cell line. |
Cell Cycle Analysis[5] | Cell Line: | Hct-116 human colon carcinoma cells | | Concentration: | 1 μM | | Incubation Time: | 3 hours and 24 hours | | Result: | Both, bolus (3 h) and continuous (24 h) incubation led to a significant reduction of cells in G0/G1 and accumulation in G2 phase. |
Western Blot Analysis[4] | Cell Line: | Breast cancer cell lines MCF-10F, MCF-7 and MDA-MB-231 | | Concentration: | 1 μM for MCF-10F and MDA-MB-231 cells, 4 μM for MCF-7 cells | | Incubation Time: | 48 hours | | Result: | Bax protein expression was upregulated in MCF-10F and MDA-MB-231 cell lines but MCF-7 cells did not show any significant increase.
Caspase-8 gene expression was upregulated in MCF-10F, but it was downregulated in MCF-7 and MDA-MB-231 cells. |
|
体内研究
(In Vivo) | Treatment with Doxorubicin (2 mg/kg) or Zoledronic acid (100 μg/kg) alone does not statistically significantly decrease final tumor volume compared with saline. Mice treated with Doxorubicin plus Zoledronic acid have statistically significantly smaller final tumor volumes than those treated with Doxorubicin alone[6].
| Animal Model: | Female MF1 nu/nu mice bearing MDA-G8 breast tumor xenograft (6-week-old)[6] | | Dosage: | Doxorubicin (2 mg/kg); Zoledronic acid (100 μg/kg) | | Administration: | Intravenous injection; once a week; 6 weeks | | Result: | Moderate inhibition of subcutaneous tumor growth in mice that were treated with 2 mg/kg Doxorubicin alone or with 100 μg/kg Zoledronic acid alone compared to the saline control.
Mice treated with Zoledronic acid and Doxorubicin together had statistically significant smaller mean tumor volumes on day 42 than those treated with Doxorubicin alone. |
|
| Clinical Trial | |
| 分子量 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 中文名称 | |
| 结构分类 | |
| 来源 | Streptomyces peucetius var. Caesius |
| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
| 溶解性数据 | In Vitro: DMSO : 35.71 mg/mL(61.57 mM;ultrasonic and warming and heat to 60℃) H2O : 20 mg/mL(34.48 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.7242 mL | 8.6210 mL | 17.2420 mL | | 5 mM | 0.3448 mL | 1.7242 mL | 3.4484 mL | | 10 mM | 0.1724 mL | 0.8621 mL | 1.7242 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture and light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 5% DMSO 40%PEG300 5%Tween-80 50% saline Solubility: ≥ 2.75 mg/mL (4.74 mM); Clear solution 2. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (3.59 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.59 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 3. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (3.59 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (3.59 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
|
