Selective inhibitors of nuclear export block pancreatic cancer cell proliferation and reduce tumor growth in mice.

ABSTRACT:

Background & aims

Tumor-suppressor proteins are inactivated by many different mechanisms, including nuclear exclusion by chromosome region maintenance (CRM)-1. Increased tumor levels of CRM-1 have been correlated with poor prognosis of patients with pancreatic cancer, making it a therapeutic target. Selective inhibitors of nuclear export (SINEs) bind to CRM-1 to irreversibly inhibit its ability to export proteins; we investigated a new class of SINEs in pancreatic cancer cells.

Methods

We studied the effects of SINE analogs in a panel of pancreatic cancer cell lines and nontransformed human pancreatic ductal epithelial cells using proliferation, apoptosis, immunoblot, co-immunoprecipitation, small inhibitor RNA, and fluorescence microscopy analyses. The effects of the SINEs

SUBMITTER: Azmi AS 

PROVIDER: S-EPMC3594519 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature