Secretory leukocyte protease inhibitor antagonizes paclitaxel in ovarian cancer cells.

ABSTRACT:

Purpose

Ovarian cancer recurrence with the development of paclitaxel resistance is an obstacle to long-term survival. We showed that secretory leukocyte protease inhibitor (SLPI) is a survival factor for ovarian cancer. We hypothesize that SLPI may antagonize paclitaxel injury.

Experimental design

Differential SLPI induction in response to paclitaxel and in response to stable forced expression of SLPI was shown in A2780-1A9 cells and their paclitaxel-resistant sublines, PTX10 and PTX22, and confirmed with HEY-A8 cells. SLPI-mediated survival was reduced by the MAP/extracellular signal-regulated kinase (ERK) kinase inhibitor, U0126, and a humanized neutralizing monoclonal anti-SLPI antibody, CR012. OVCAR3 xenographs tested the role of CR012 in vivo.

Results

SLPI expres

SUBMITTER: Rasool N 

PROVIDER: S-EPMC2808000 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature