1.Differential gene expression profiles in paclitaxel-induced cell cycle arrest and apoptosis in human breast cancer MCF-7 cells.
Jin WANG ; Fang-ting HE ; Chi-hung TZANG ; Wang-fan FONG ; Pei-gen XIAO ; Rui HAN ; Meng-su YANG
Acta Pharmaceutica Sinica 2005;40(12):1099-1104
AIMTo elucidate the molecular mechanism of cell cycle arrest and apoptosis of MCF-7 cells induced by paclitaxel.
METHODSFlow cytometry was used to determine the cell cycle changes of MCF-7 cells upon paclitaxel treatment. Gene expression profiles of MCF-7 cells induced by paclitaxel were obtained by using cDNA microarrays containing 9984 genes and expressed sequence tags (ESTs).
RESULTSCell cycle analysis showed that 77.8% of cells arrested at G2/M phase and 1.3% of cells underwent apoptosis upon 100 nmol x L(-1) paclitaxel treatment for 24 hours; cDNA microarray results revealed that 27 and 77 genes were differentially expressed upon 12.5 nmol x L(-1) (IC50) and 100 nmol x L(-1) paclitaxel treatment, respectively.
CONCLUSIONPaclitaxel stabilized microtubules and caused G2/M cell cycle arrest and apoptotic cell death in a concentration-dependent manner, which is associated with the regulation of selected genes related to microtubule assembly and cytoskeleton, cell cycle regulation, and DNA repair and apoptosis.
Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; genetics ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; DNA Repair ; drug effects ; Dose-Response Relationship, Drug ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Paclitaxel ; administration & dosage ; pharmacology