Journal
DIGESTIVE DISEASES AND SCIENCES
Volume 57, Issue 8, Pages 2072-2078Publisher
SPRINGER
DOI: 10.1007/s10620-012-2132-5
Keywords
Pancreatic cancer; RAP80; Gemcitabine; Apoptosis
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Receptor-associated protein 80 (RAP80) increases substantially in pancreatic cancer. The involvement of RAP80 in the chemoresistance of pancreatic cancer should be elucidated. We investigated the effects of inhibiting RAP80 expression on the sensitivity of pancreatic cancer cells to gemcitabine chemotherapy by using small interfering RNA (siRNA). Chemically synthesized siRNA RAP80 was transfected into human pancreatic cancer cell lines SW1990 and Capan-2. The IC50 of gemcitabine was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell apoptosis was detected by using flow cytometry. Expression of apoptosis-related genes, Bax, Bcl-2, TRAIL, survivin, and caspase-8 was detected by using reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Gemcitabine inhibits proliferation of SW1990 and Capan-2 cells in a concentration-dependent manner. Inhibition of RAP80 expression significantly reduced the IC50 of gemcitabine (P < 0.01). RAP80 siRNA combined with gemcitabine significantly increased (P < 0.01) apoptosis of pancreatic cancer cell lines SW1990 and Capan-2, increased expression of Bax mRNA, reduced Bcl-2 mRNA expression (P < 0.01), and slightly increased TRAIL mRNA expression (P < 0.01). Correspondingly, in the RAP80 siRNA combined with gemcitabine group, both Bax and cleaved caspase-8 protein levels were increased (P < 0.01), whereas Bcl-2 protein decreased significantly (P < 0.01). No change in survivin mRNA expression was observed (P < 0.01). Inhibition of RAP80 expression can induce apoptosis in pancreatic cancer cells and improve chemosensitivity to gemcitabine.
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