Overexpression of CXCL10 in human prostate LNCaP cells activates its receptor (CXCR3) expression and inhibits cell proliferation
Overexpression of CXCL10 in human prostate LNCaP cells activates its receptor (CXCR3) expression and inhibits cell proliferation
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DOI：
10.1016/j.bbadis.2006.06.017
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发表时间：
2006-09-01
影响因子：
6.2
通讯作者：
Lin, Tu
中科院分区：
文献类型：
--
作者：
Nagpal, Madan L.;Davis, Jeffrey;Lin, Tu
慢性或复发性炎症在包括前列腺癌在内的许多类型癌症的发展中起作用。CXCL 10（interferon-gamma inducible protein-10，IP-10）是一种分子量为8.7 kDa的分泌性小蛋白。最近，已经显示与前列腺癌细胞（CA-HPV-10和PC-3）相比，正常前列腺上皮（PZ-HPV-7）细胞产生较低量的血管生成CXC趋化因子（GRO-α，IL-8）和较高量的血管抑制趋化因子（CXCL 10，CXCL 11）。因此，我们研究了CXCL 10过表达在人前列腺癌LNCaP细胞中的作用。用pIRES 2-EGFP载体中的CXCL 10 cDNA瞬时转染LNCaP细胞。通过半定量常规和定量实时RT-PCR和荧光激活细胞分选（FACS）测定CXCL 10、CXCR 3、PSA和G3 PDH mRNA水平。转染细胞中CXCL 10在mRNA和蛋白水平上的表达显著增强。CXCL 10的过表达抑制了转染细胞在血清限制性培养基（含1%FCS的RPMI 1640培养基）中的增殖，抑制率为30%~ 40%，并降低了PSA的产生。RT-PCR和流式细胞仪检测显示，CXCL 10的过表达可显著诱导CXCR 3的表达。这些结果表明，CXCL 10通过上调CXCR 3受体抑制LNCaP细胞增殖并减少PSA产生。CXCL 10在前列腺癌的治疗中可能是潜在有用的。(c)2006 Elsevier B. V.保留所有权利。
Chronic or recurrent inflammation plays a role in the development of many types of cancer including prostate cancer. CXCL10 (interferon-gamma inducible protein-10, IP-10) is a small secretory protein of 8.7 kDa. Recently, it has been shown that normal prostate epithelial (PZ-HPV-7) cells produce lower amounts of angiogenic CXC chemokines (GRO-alpha, IL-8) and higher amounts of angiostatic chemokines (CXCL10, CXCL11) as compared to prostate cancer cells (CA-HPV-10 and PC-3). Accordingly, we studied the effects of overexpression of CXCL10 in human prostate cancer LNCaP cells. LNCaP cells were transiently transfected with CXCL10 cDNA in pIRES2-EGFP vector. CXCL10, CXCR3, PSA and G3PDH mRNA levels were determined by semi-quantitative conventional and quantitative real-time RT-PCR and fluorescence-activated cell sorting (FACS). The expression of CXCL10 was markedly enhanced in the transfected cells at mRNA and protein levels in the cells. Overexpression of CXCL10 inhibited cell proliferation of the transfected cells by 30%-40% in serum-limited medium (1% FCS in RPMI1640 medium) and decreased PSA production. CXCR3 expression was significantly induced by the overexpression of CXCL10 as determined by RT-PCR and FACS. These results indicated that CXCL10 inhibited LNCaP cell proliferation and decreased PSA production by up-regulation of CXCR3 receptor. CXCL10 may be potentially useful in the treatment of prostate cancer. (c) 2006 Elsevier B.V. All rights reserved.