| Docetaxel is a anti-cancer agent, reversibly binds to microtubules, such as β- tubulin, mainly for the treatment of breast, ovarian, prostate, and non-small cell lung cancer. Docetaxel is a semi-synthetic analogue of paclitaxel (Taxol), an extract from the bark of the rare Pacific yew tree Taxus brevifolia. Upon entering of a cancer cell into mitosis, docetaxel will promote the polymerization and inhibit the depolymerization of microtubules causing a mitotic arrest.[1] The IC50 values of docetaxel are ??.2 μM, 0.64, ??.12 and 3.5 nM in human gastric cancer cell lines MKN-7, MKN-28, MIZN-45 and NUGC-4, respectively. The IC50 values of docetaxel are 4.0, 0.94, 99, 0.39 and 0.5 nM in five cultured human gastric cancer cell lines KATO-III, KKLS, ST-SA-1, NAKAJIMA and ST-KM, respectively.[2] The colony forming ability of SMMC-7721 cells decreases gradually with increasing dose of docetaxel treatment, and the colony forming inhibition rate attains 100 % with IC50 value of 0.5 nM. Furthermore, docetaxel (10 nM for 24 hours) induces a marked apoptosis. Docetaxel causes SMMC-7721 cells G2/M phase arrest mainly at 100 nM and 1 μM, at 1 μM the G2/M phase cells account for 96.10%. In comparison with the control group, the SMMC-7721 cells ROS level increases by 1.69, 1.78 and 1.80 times after treatment with 0.25, 0.5 and 10 nM docetaxel, respectively.[3] In human gastric cancers (MKN-28, MKN-45 and KKLS) xenografts, docetaxel inhibits tumour growth dose-dependently, particularly at doses of 22 and 15 mg/kg when complete tumour regression is observed in all mice. Tumour regression rates is 98% at 7.5 mg/kg and 47% at 3.75 mg/kg for MKN-28 xenograft. As a side-effect of docetaxel, body weight is decreased by 18% in the treatment period at a dose of 22 mg/kg, but no mice are sacrificed due to treatment-related toxicity.[2] In vivo cytotoxicity experiments, the IC50 for docetaxel is approximately 2 and 40 nM for PC-3 cells and MLL cells (the Dunning rat R2237 metastatic anaplastic to lymph node, lung subline), respectively. The addition of 100 nM of estramustine does not significantly alter the IC50 for any docetaxel dose in PC-3 cells. However, the addition of 100 nM of estramustine lowers the IC50 of docetaxel to approximately 15 nM in MLL cells. In vivo animal MLL cells tumor model, low-dose docetaxel (7 mg/kg) with estramustine demonstrates antineoplastic activity similar to that of high-dose docetaxel (11.6 mg/kg) alone, suggesting additive activity between the drugs.[4] |
