Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.

ABSTRACT. Forkhead box protein O1 (FOXO1) is an important transcriptional regulator of cell proliferation, and is considered essential for tumor growth and progression. However, the function of FOXO1 in human cervical cancer remains unclear. In this study, we investigated the role of FOXO1 in cervical cancer. Our results showed that FOXO1 expression was lower in cervical cancer than in cervical intraepithelial neoplasia and normal cervix by immunohistochemical analysis (P < 0.05). The level of FOXO1 in high-grade lesions was significantly lower than in low-grade lesion (P < 0.05), indicating that deficient expression of FOXO1 is involved in tumor progression and significantly associated with late-stage tumors (P < 0.05), which was further supported by clinicopathological, real-time polymerase chain reaction, and Western blotting analysis. Moreover, we confirmed that the overexpression of FOXO1 remarkably repressed cell growth and blocked cell proliferation, accompanied by cell-cycle arrest in the G 2 /M phase and upregulation of caspases-3 and -9 gene expression. Collectively, our data suggest that FOXO1 plays a vital role in inhibiting cervical cancer development by inducing cell-cycle arrest 6605-6616 (2015) and apoptosis. FOXO1 expression is a favorable prognostic factor for human cervical cancer.

CXCL3 belongs to the CXC-type chemokine family and is known to play a multifaceted role in various human malignancies. While its clinical significance and mechanisms of action in uterine cervical cancer (UCC) remain unclear. This investigation demonstrated that the UCC cell line HeLa expressed CXCL3, and strong expression of CXCL3 was detected in UCC tissues relative to nontumor tissues. In addition, CXCL3 expression was strongly correlated with CXCL5 expression in UCC tissues. In vitro, HeLa cells overexpressing CXCL3, HeLa cells treated with exogenous CXCL3 or treated with conditioned medium from WPMY cells overexpressing CXCL3, exhibited enhanced proliferation and migration activities. In agreement with these findings, CXCL3 overexpression was also associated with the generation of HeLa cell tumor xenografts in athymic nude mice. Subsequent mechanistic studies demonstrated that CXCL3 overexpressing influenced the expression of extracellular signal-regulated kinase (ERK) signaling pathway associated genes, including ERK1/2, Bcl-2, and Bax, whereas the CXCL3-induced proliferation and migration effects were attenuated by exogenous administration of the ERK1/2 blocker PD98059. The data of the current investigation support that CXCL3 appears to hold promise as a potential tumor marker and interference target for UCC. K E Y W O R D Scervical cancer, CXCL3, ERK, malignant behavior, upregulation

Abstract. serves an important function in chronic inflammation and cancer development; however, the underlying molecular mechanism(s) of IL-8 in uterine cervical cancer remains unclear. The present study investigated whether IL-8 and its receptors [IL-8 receptor (IL-8R)A and IL-8RB] contributed to the proliferative and migratory abilities of HeLa cervical cancer cells, and also investigated the potential underlying molecular mechanisms. Results demonstrated that IL-8 and its receptors were detected in HeLa cells, and levels of IL-8RA were significantly increased compared with those of IL-8RB. Furthermore, the level of IL-8 in cervical cancer tissues was significantly increased compared with that in normal uterine cervical tissues, and migratory and proliferative efficiencies of HeLa cells treated with exogenous IL-8 were increased, compared with untreated HeLa cells. In addition, exogenous IL-8 was able to downregulate endocytic adaptor protein (NUMB), and upregulate IL-8RA, IL-8RB and extracellular signal-regulated protein kinases (ERKs) expression levels in HeLa cells. Results suggest that IL-8 and its receptors were associated with the tumorigenesis of uterine cervical cancer, and exogenous IL-8 promotes the carcinogenic potential of HeLa cells by increasing the expression levels of IL-8RA, IL-8RB and ERK, and decreasing the expression level of NUMB.

ABSTRACT. Tumor necrosis factor-α (TNF-α) is an important proapoptotic cytokine, which performs a broad range of immune and inflammatory functions in several vital processes. TNF-α-induced apoptosis has been confirmed, however, relatively little is known regarding the role of forkhead box class-O 1 (FOXO1) in mediating TNF-α-induced apoptosis in cervical cancer. In our study, we used the well-characterized cervical cancer cell line C-33A to investigate the role of FOXO1. The results showed that the antitumor agent TNF-α increased the expression level of FOXO1 (P < 0.05) and enhanced its transcriptional activity (P < 0.05). Furthermore, knockdown of FOXO1 repressed TNF-α-induced apoptosis and caspase-3, 8, and 9 expressions (P < 0.05). Collectively, these findings suggest that TNF-α upregulated the transcriptional factor FOXO1, leading to an increased expression of apoptotic gene, which leads to an increase in apoptosis.