| 名稱 | Docetaxel |
| 描述 | Docetaxel (RP-56976) is a semi-synthetic analog of paclitaxel, a microtubule depolymerization inhibitor (IC50=0.2 μM). Docetaxel attenuates the effects of bcl-2 and bcl-xL gene expression and exhibits apoptosis-inducing, anti-tumor activity. |
| 細(xì)胞實(shí)驗(yàn) | NCI-H460 cells (4 × 10^3) were grown in 100 μl of DMEM medium containing serum per well in a 96-well plate. After 24 h, the cells were treated with docetaxel (0, 0.2, 0.63, 2, 6.3, 20, 63 and 200 nmol/L, respectively) for 72 h. Every treatment was triplicate in the same experiment. Then 20 μl of MTS was added to each well for 1 to 4 h at 37°C. After incubation, the absorbance was read at a wavelength of 490 nm according to the manufacturer's protocol. The IC50 calculation was performed with GraphPad Prism 5.0 software [2]. |
| 動(dòng)物實(shí)驗(yàn) | Docetaxel (0, 10, 20, 30, 40, 60, and 80 mg/kg per week) was given once a week for 3 weeks for mice. Because more than 30 mg/kg per week of the drug caused body weight loss in mice, 20 mg/kg per week of docetaxel was judged to be the maximum nontoxic dose. Docetaxel (20 mg/kg per week) was given to mice once a week for 3 weeks at one of the following different points (2, 10, 14, or 22 HALO). Seventy-two hours after the final dosing of the agent, the intestinal mucosa of the small intestine (proximal 8 cm) was removed, fixed in 20 N Mildform solution (containing 8% formaldehyde in a buffered solution), and embedded in paraffin blocks, and sections of 5 mm were put on glass slides. Apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method, using the Apop Tag Peroxidase In Situ Apoptosis Detection Kit. Specimens were dewaxed and immersed in phosphate-buffered saline for 5 minutes at room temperature, incubated with 20 mg/ml proteinase K for 15 minutes at room temperature, and then quenched of endogenous peroxidase in 2% hydrogen peroxide in phosphate-buffered saline. Terminal deoxynucleotidyl transferase enzyme was applied directly onto the specimens, which were then incubated at 37°C for 1 hour. The reaction was terminated by transferring the slides to stop/wash buffer for 10 minutes at room temperature, and then specimens were covered with peroxidase-conjugated anti-digoxigenin antibody and incubated for 30 minutes at room temperature. Specimens were then soaked in staining buffer containing 0.05% diaminobenzidine to achieve color development. Finally, the specimens were counterstained by immersion in Mayer's hematoxylin solution. Apoptotic cells were counted under a light microscope in a good longitudinal crypt section. Starting at the base of the crypt column, the TUNEL-positive cells were counted up to the 18th cell position in each crypt.One hundred crypt sections were scored in each animal, and a frequency of TUNELpositive cells per crypt was calculated. Dosing time-dependent influence of docetaxel on intestinal apoptosis was also examined in female Balb/c mice [5]. |
| 體外活性 | 方法：人肺癌細(xì)胞 NCI-H460 用 Docetaxel (0.2-200 nmol/L) 處理 24-72 h，使用 MTS 方法檢測細(xì)胞活力。
結(jié)果：NCI-H460 在 72 h 時(shí)對 Docetaxel 的 IC50 為 0.030 μmol/L，24 h 時(shí)為 0.116 μmol/L。[1]
方法：人前列腺癌細(xì)胞 PC-3、DU-145 和 LNCaP 用 Docetaxel (0.5-4 nM) 處理 48 h，使用 Flow Cytometry 檢測細(xì)胞凋亡情況。
結(jié)果：高劑量 Docetaxel 處理顯著增加了 Annexin V+ 凋亡細(xì)胞的比例。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 Docetaxel (5-10 mg/kg) 和 PD-1 inhibitor (200 μg/只) 腹腔注射給攜帶小鼠前列腺癌腫瘤 RM-1 的 CB17 SCID 小鼠，每周五次，持續(xù)十天。
結(jié)果：PD-1 inhibitor 聯(lián)合 Docetaxel 對小鼠前列腺癌具有協(xié)同作用，抑制了前列腺腫瘤的生長，提高了存活率并減少了不良反應(yīng)。[3]
方法：為檢測體內(nèi)抗腫瘤活性，將 Docetaxel (7.5-15 mg/kg，瘤內(nèi)注射 IT，每周兩次，持續(xù)六周；或每周 20-40 mg/kg，靜脈注射 IV) 給藥給攜帶 HNSCC 腫瘤 HN30 或 HN12 的 C57BL/6 小鼠。
結(jié)果：IT Docetaxel 提高了整體存活率和無病生存率，并逆轉(zhuǎn)了腫瘤生長。在同等劑量水平下，IT Docetaxel 的腫瘤峰值濃度比 IV 治療高 26 倍，腫瘤暴露時(shí)間比 IV 治療長 24 倍。[4] |
| 存儲(chǔ)條件 | keep away from direct sunlight,keep away from moisture,store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 80.8 mg/mL (100 mM)
DMSO : 60 mg/mL (74.27 mM)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 8.08 mg/mL (10 mM), Suspension. Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
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| 關(guān)鍵字 | Docetaxel | NSC628503 | Endogenous Metabolite | inhibit | Inhibitor | Apoptosis | RP 56976 | RP56976 | NSC-628503 | Microtubule/Tubulin |
| 相關(guān)產(chǎn)品 | Formamide | Guanidine hydrochloride | Naringin | Daidzein | Glycerol | Sucrose | Ferulic Acid | Stavudine | Thymidine | Fumaric acid |
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