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

被引:22
作者
Zhang, Mingjie [1 ]
Ding, Guoping [1 ]
Zhou, Liangjing [1 ]
Shen, Tao [1 ]
Xu, Xiaodong [1 ]
Zhao, Ting [1 ]
Jia, Shengnan [1 ]
Cao, LiPing [1 ]
机构
[1] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Surg, 3 Qingchundong Rd, Hangzhou 310020, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
interferon-gamma; pancreatic cancer; CXCL8 (IL-8); RhoGDI2 (ARHGDIB); NF-kappa B; IFN-GAMMA; INTERLEUKIN-8; STATISTICS; APOPTOSIS; GROWTH; EXPRESSION; INVASION; RECEPTOR; FACES;
D O I
10.1089/jir.2018.0070
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:413 / 422
页数:10
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