Abstract 520: Alteration of chemokine gene expression in PC-3 cells treated with NSAIDs

Abstract

Abstract Background: The role of chronic inflammation for developing prostate cancer and its progression to metastasis is supported by increasing evidence. Among the pro-inflammatory regulators that seem to play a critical function in prostate tumorigenesis, the most implicated have been the members of the CXC chemokines and their receptors, which have been deemed as significant players in several of the critical steps in tumorigenesis and/or metastasis. CXC chemokines have been classified into two subclasses, ELR+ and ELR−. Most of the ELR+ CXC chemokines are angiogenic, while most of the ELR- are anti-angiogenic. Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk of several cancers, including prostate cancer (PCa). The protective effect of NSAIDs has been attributed to inhibition of cancer metastasis. The aim of this work was to determine the expression profiles of the CXC chemokines in the metastatic prostatic cancer cell line PC-3 compared to the non-tumorigenic PWR-1E cell line and to evaluate the effects of NSAIDs in the expression patterns of these molecular components. Methods: Differences in gene expression were determined between highly metastatic PC-3 cells and the non-tumorigenic PWR-1E by qRT-PCR and ELISA for a panel of 13 genes encoding CXC chemokines: ELR+ (CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, and CXCL8) and ELR- (CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL14). Changes in the expression of these genes in response to treatment with NSAIDs (ibuprofen and nimesulide) were also determined. Results: Highly metastatic PC-3 cells showed high expression levels of six ELR+ CXC chemokines: CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, and CXCL8; there was no detectable expression for CXCL7. In contrast, expression of ELR- CXC chemokines (CXCL9, CXCL10, CXCL11, and CXCL14) was not detected in either PC-3 or PWR-1E cells. The expression levels of CXCL4 and CXCL12 were comparable in the two cell lines. Treatment of PC-3 cells with ibuprofen and nimesulide affected the expression pattern of the genes evaluated in these cells. Ibuprofen treatment caused decreased expression of ELR+ CXCL6 in PC-3 cells; this effect was not seen with nimesulide treatment. Ibuprofen and Nimesulide treatments caused an increased expression of ELR+ CXCL5 and CXCL8 chemokines. The expression levels of the remaining CXC chemokines: CXCL1, CXCL2, CXCL3, CXCL4, and CXCL12 were not affected by treatment with the NSAIDs assayed. Conclusions: Highly metastatic PC-3 cells had increased expression levels of ELR+ CXC chemokines compared to non-tumorigenic PWR-1E cells. NSAIDs (Nimesulide and ibuprofen) caused differential changes in the pattern of CXC chemokine expression of PC-3 cells. Pharmacological effects of NSAIDs in prostate cancer warrants further investigation at the clinical settings. Additional studies are required to determine the clinical usefulness of NSAIDs in prostate cancer. Citation Format: Niradiz Reyes, Juan Rebollo, Raj Tiwari, Jan Geliebter. Alteration of chemokine gene expression in PC-3 cells treated with NSAIDs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 520.