Interferon Gamma Inhibits CXCL8-Induced Proliferation and Migration of Pancreatic Cancer BxPC-3 Cell Line via a RhoGDI2/Rac1/NF-κB Signaling Pathway

Interferon gamma (IFN-) is a dimeric soluble cytokine and the only type II interferon. Accumulated evidence suggests that IFN- inhibits tumor progression. This study investigated the effects of IFN- on the proliferation and migration of pancreatic cancer (PC) cells and the underlying mechanism. IFN- treatment decreased the expression and secretion of CXCL8 in BxPC-3 PC cells, suppressed the proliferation and migration of these cells, and enhanced their apoptosis, as determined by increased levels of cleaved Caspase-8 and Bax together with reduced expression of Bcl-2. These effects were abolished by overexpression of CXCL8. Moreover, IFN- treatment downregulated RhoGDI2 expression. Depletion of RhoGDI2 and Rac1 by using small interfering RNAs and inhibition of NF-B by BMS-345541 (an IB kinase [IKK] inhibitor) suppressed expression of CXCL8. Our results indicate that IFN- inhibits the proliferation and migration of PC cells by suppressing CXCL8 expression via a RhoGDI2/Rac1/NF-B signaling pathway.