Effects Of Docetaxel On The Phenotype Of Human Mucoepidermoid Carcinoma M3SP4 Cells In Vitro And In Vivo

The effects of Docetaxel on the phenotype of human mucoepidermoid carcinoma MaSP4 cells were investigated with cell counting, colonogenic assay, flow cytometry, morphological observation, immunohistochemical staining, tumor growth and metastasis experiments in nude mice. Following results were obtained:1. Docetaxel inhibited the MaSP4 cells growth in a dose-dependent and time-dependent manner at the comparatively low concentration and with the exposure time for more than 12h. The IC30 and IC50 values for 72h-exposure were 0.34nmol/L and 0.63nmol/L respectively, RAA was 5527.2. Following changes were observed after the M3S?4 cells had been exposed to Docetaxel:.(1) Prolongation of DT from 32.7h to 43h; (2) Decrease of clonogenesity, the clonogenesity(%) of the control group and of the cells treated with Docetaxel at 0.05nM, O.lnM and 0.34nM were 29.2?.4% and 20.2?.8%,2.8?.4% and 0%, respectively. (3) Increase of the cell number in the phase and decrease of that in GI+GO phase, the percentage of GI, S and Ga of control group and were 69.4, 24.5 and 6.1, the percentage of GI, S and 62 of the cells treated with ICao were 63.3, 25.9 and 10.8, respectively. Appearance of the sub-Gl peak (4) Multi-nuclei cells and gigantic-nucleus cells , retrograde degeneration, apoptosis; (5) Decrease of protein expression of bcl-2 and increase of that of p53 and nm23-Hl;3. Decrease of tumor growth and metstatic capability in vivo, the weight(g) of tumor in submandibular gland treated with the drug at 30mg/kg-week and in the control group were 0.31?.05 and 1.20?.23, respectively. The growth inhibition was 183.6; the number of metastatic foci in the two groups on lung surface in the nude mice were 0 and 11 ?.4, respectively. The metastasis inhibition was 100%.Docetaxel may arrest the MjSP4 cells at G2/M phase of the cell cycle through the ability of promoting tublin assemble and stabilizing microtubule and prevent the mitiotic progression; it induces apoptosis by inhibiting the protection for the cells by bcl-2. Cytotoxicity to tumor cells also plays a great role in its anti-tumor capacity. Docetaxel can inhibit the function of VEGF leading to the decrease of angiogenesis which can attribute to the decrease of the growth and metastasis potential of the tumor. Docetaxel may be a promising agent in the treatment of mucoepidermoid carcinoma of salivary gland.