Polymeric delivery of siRNA for dual silencing of Mcl-1 and P-glycoprotein and apoptosis induction in drug-resistant breast cancer cells

摘要: Enhanced survival mechanisms of malignant cells in combination with elevated levels drug transporters can sustain an undesirable resistance against therapy. Short interfering RNA (siRNA) delivery targets involved aberrant is a promising approach and we hypothesize that simultaneous silencing multiple could prove more advantageous than common to silence individual targets. To explore this approach, targeted anti-apoptotic proteins myeloid cell leukemia 1 (Mcl-1) survivin along the efflux pump P-glycoprotein (P-gp) drug-resistant breast cancer cells. Polymeric siRNA was employed for purpose by using small polyethylenimine (PEI) substituted lipids. While Mcl-1 caused ∼90% death wild-type cells, effect less significant P-gp over-expressing An additive evident latter where these created significantly higher compared each target. Prolonged exposure doxorubicin (DOX) resulted upregulation P-gp, protein, Mcl-1. Dual again resistance-induced which displayed increased dependency on survival. Cytotoxic DOX also enhanced after We conclude polymer-mediated simultaneously reverse resistance.