Reversal of paclitaxel-chemoresistance by mixed Pluronic P105/L101 micelles in human ovarian cancer SKOV-3/PTX cells

Abstract

A mixed Pluronic micelle for delivery of paclitaxel (PTX) with Pluronic P105 and L101 was capable of sensitizing resistant SKOV-3/PTX tumor cells. A significant inhibition of P-gp efflux system was observed in the range of monomer or micelle concentrations of the mixed Pluronics in the resistant tumor cells. Importantly, the mixed micellar PTX also showed enhanced apoptotic effect, and drastically changed the pharmacogenomic responses to free PTX. It was found that some important genes for apoptosis induction, such as BCL-2 antagonist and death domain receptor, displayed elevated levels; some cell cycle-arresting genes, such as cyclins, cyclin-dependent kinase regulator, cullin and forhead box M, showed significant down-regulated levels; and some clinical prognostic genes for resistance to chemotherapy and metabolism, such as drug efflux pump and cytochrome P450, were also down-regulated. It is concluded that inhibition of P-gp efflux system, enhanced induction of apoptosis, and significant changes of expression profiles of apoptosis, resistance and cell cycle arresting-related genes were responsible for PTX-resistance reversal by the mixed Pluronic P105/L101 micelles in the SKOV-3/PTX tumor cells.