生物活性

Epirubicin HCl, the hydrochloride folm of epirubicin(EPI), a member of the anthracycline family, is widely used in breast cancer. Epirubicin Hydrochloride is a cell-permeable antitumor antibiotic. Inhibits the synthesis and function of DNA (IC50 = 62.7 μM in rat glioblastoma cell lines) and inhibits the relaxing property of topoisomerase II. A stereoisomer of Doxorubicin that exhibits reduced cardiotoxicity. Epirubicin Hydrochloride's antitumor actions are mediated by targeting and inhibiting Topo II (topoisomerase II).

体外研究

体内研究

激酶实验

细胞实验

Hep G2 cell line[1]

The Hep G2 cells were routinely cultured inDMEM supplemented with 10% fetal calf serum, 1% antibiotic-antimycotic solutionin a humidified atmosphere containing 5% CO₂ at 37°C. For subculturing,cells were harvested after trypsin/EDTA treatment at 37°C. Cells were used whenmonolayer confluence had reached 75%. Hep G2 cells treated with epirubicin HCland epirubicin HCl + SOD were used as experimental groups. Untreated Hep G2cells were used as a control group.

EpirubicinHCl

IC50of epirubicin HCl (the concentration of a drug that inhibits cellgrowth by 50%) was calculated for Hep G2 cells during three periods ofincubation (24, 48 and 72 h). Hep G2 cells were treated with epirubicin HCl inthe medium.

MTTassay

Hep G2 cells (500 cells/well, monolayer)were plated in a 96-well plate. The next day the cells were treated withepirubicin HCl in the medium. The data were expressed as average valuesobtained from eight wells for each concentration (0.05 μg/ml, 0.1μg/ml, 0.4μg/ml, 0.8μg/ml, 1.2μg/ml, 1.6 μg/ml, 2.4μg/ml, 3.0μg/ml, 5.0μg/ml, 8.0μg/ml, 10.0μg/ml and 12.0μg/ml). At the end of the incubation periods (24, 48 and 72 h), thecytotoxicity of epirubicin HCl on Hep G2 cells was determined by the MTT assay.Tetrazolium salts such as MTT are metabolized by mitochondrial dehydrogenases toform a blue formazan dye and are, therefore, useful for the measurement ofcytotoxicity. Test reagents were added to the culture medium. Briefly, 15%volume of dye solution was added to each well after the appropriate incubation time.After 1 h of incubation at 37°C, an equal volume of solubilization/stopsolution (dimethylsulfoxide) was added to each well for additional 1 h incubation.The absorbance of the reaction solution at 570 nm was recorded. The absorbanceat 630 nm was used as a reference. The net wastaken as the index of cell viability. The reading taken from the wells withcells cultured with the control medium was used as a 100% viability value. Thepercent viability was calculated by the formula The IC50 value of epirubicin HCl in MTT assay was calculatedas 1.6μg/ml for 24 h incubation. Preincubation of Hep G2 cells with SOD(100μg/ml) for 30 min, before epirubicin HCl (1.6 μg/mlfor 24 h) treatment resulted in 93% Hep G2 cell viability.

动物实验

Animals[2]

Female BALB/c mice (8 weeks, weighting 18to 22 g) were housed in a specified chamber with controlled air conditions(temperature 20–25 °C, humidity 50–65 %) and free access to sterile food andwater.

Invivo antitumor effects

A 4T1 cell suspension (100μL, 5× 10⁶ cells/mL) was injected subcutaneously into the right side of the fourth mammarygland of each mouse. The tumor length (L) and width (W) were measured everyother day, and the tumor volume was calculated by using the following formula:V (mm³) = (L ×W²) / 2. On day 8 of 4T1 cells injection, thesize of tumors was approximately 100 mm³. Mice were randomly dividedinto four groups and accepted treatments every other day for eight times:

1. Control group (Cont, n = 8): micereceived intragastrically administered (i.g.) and a tail intravenous injectionof saline.

2. Pae (paeonol) group (n =8): micereceived i.g. Pae (200 mg/kg) and a tail intravenous injection of saline.

3. EPI (epirubicin) group (n= 8): micereceived i.g. saline and a tail intravenous injection of EPI (2.5 mg/kg).

4. Pae + EPI group (n = 8): mice receivedi.g. Pae (200 mg/kg) and a tail intravenous injection of EPI (2.5 mg/kg).

The mice weights were recorded every otherday. Bloodwas collected and the mice were sacrificed after 16 days. The tumors,hearts, and other tissues were removed rapidly and weighed. Several tissueswere fixed in formalin for hematoxylin-eosin (HE) staining, TdT-mediated dUTPnickend labeling (TUNEL), and immunohistochemistry (IHC), whereas others wererapidly frozen in liquid nitrogen and stored in −80 °C for Western blotting(WB) analysis.

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Cersosimo RJ, et al. J Clin Oncol, 1986, 4(3), 425-439.
[2] Bonadonna, G., et al., Drugs ten years later: epirubicin. Ann Oncol, 1993.
[3] Ozkan, A. and K. Fiskin, Epirubicin HCl toxicity in human-liver derived hepatoma G2 cells. Pol J Pharmacol, 2004.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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