PubMed | Shandong University, Linyi Peoples Hospital Linyi, Peoples Hospital of Rizhao Rizhao, Central Hospital of Yishui Linyi and 2 more.
Type: Journal Article | Journal: International journal of clinical and experimental pathology | Year: 2015
Identifying prognostic factors for osteosarcoma (OS) aids in the selection of patients who require more aggressive management. XB130 is a newly characterized adaptor protein that was reported to be a prognostic factor of certain tumor types. However, the association between XB130 expression and the prognosis of OS remains unknown. In the present study, we investigated the association between XB130 expression and clinicopathologic features and prognosis in patients suffering OS, and further investigated its potential role on OS cells in vitro and vivo. A retrospective immunohistochemical study of XB130 was performed on archival formalin-fixed paraffin-embedded specimens from 60 pairs of osteosarcoma and noncancerous bone tissues, and compared the expression of XB130 with clinicopathological parameters. We then investigate the effect of XB130 sliencing on invasion in vitro and lung metastasis in vivo of the human OS cell line. Immunohistochemical assays revealed that XB130 expression in OS tissues was significantly higher than that in corresponding noncancerous bone tissues (P=0.001). In addition, high XB130 expression more frequently occurred in OS tissues with advanced clinical stage (P=0.002) and positive distant metastasis (P=0.001). Moreover, OS patients with high XB130 expression had significantly shorter overall survival and disease-free survival (both P<0.001) when compared with patients with the low expression of XB130. The univariate analysis and multivariate analysis shown that high XB130 expression and distant metastasis were the independent poor prognostic factor.We showed that XB130 depletion by RNA interference inhibited invasion of XB130-rich U2OS cells in vitro and lung metastasis in vivo. This is the first study to reveal that XB130 overexpression may be related to the prediction of metastasis potency and poor prognosis for OS patients, suggesting that XB130 may serve as a prognostic marker for the optimization of clinical treatments. Furthermore, XB130 is the potential molecular target for OS therapy.
PubMed | Linyi Tumor Hospital Linyi and Peoples Hospital of Rizhao Rizhao
Type: Journal Article | Journal: American journal of translational research | Year: 2016
Notch-1, a type-1 transmembrane protein, plays critical roles in the pathogenesis and progression of human malignancies, including breast cancer; however, the precise mechanism by which Notch-1 causes tumor cell invasion and angiogenesis remain unclear. Nuclear factor-B (NF-B), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) are critically involved in the processes of tumor cell invasion and metastasis, we investigated whether targeting Notch-1 could be mechanistically associated with the down-regulation of NF-B, IL-8, VEGF, and MMP-9, resulting in the inhibition of invasion and angiogenesis of breast cancer cells. Our data showed that down-regulation of Notch-1 leads to the inactivation of NF-B activity and inhibits the expression of its target genes, such as IL-8, VEGF and MMP-9. We also found that down-regulation of Notch-1 decreased cell invasion, and vice versa Consistent with these results, we also found that the down-regulation of Notch-1 not only decreased MMP-9 mRNA and its protein expression but also inhibited MMP-9 active form. Moreover, conditioned medium from Notch-1 siRNA-transfected breast cancer cells showed reduced levels of IL-8 and VEGF and, in turn, inhibited the tube formation of HUVECs, suggesting that down-regulation of Notch-1 leads to the inhibition of angiogenesis. Furthermore, conditioned medium from Notch-1 cDNA-transfected breast cancer cells showed increased levels of IL-8 and VEGF and, in turn, promoted the tube formation of HUVECs, suggesting that Notch-1 overexpression leads to the promotion of angiogenesis.We therefore concluded that down-regulation of Notch-1 leads to the inactivation NF-B and its target genes (IL-8, MMP-9 and VEGF), resulting in the inhibition of invasion and angiogenesis.
PubMed | Peoples Hospital of Weifang Weifang, Peoples Hospital of Rizhao Rizhao and Qingdao University
Type: Journal Article | Journal: International journal of clinical and experimental medicine | Year: 2015
CIP2A is a recently characterized oncoprotein which involves in the progression of several human malignancies. CIP2A is overexpressed in human ovarian cancer and regulates cell proliferation and apoptosis. This study was performed to investigate the role of CIP2A in ovarian cancer (OC) chemoresistance.Using DDP-resistant SKOV3 cells (SKOV3(DDP)), we first determined the effect of CIP2A silencing by siRNA-mediated knockdown of CIP2A on chemosensitivity in vitro; we then determined the effect of pCDNA3.1-mediated overexpression of CIP2A on chemosensitivity in SKOV3 cells in vitro. To elucidate the molecular mechanisms underlying CIP2A-mediated chemoresistance, the activities of AKT signaling molecules associated with CIP2A were analyzed.Knockdown of endogenous CIP2A in SKOV3(DDP) cells resulted in the reduction in cell growth and increase in the chemosensitivity of SKOV3(DDP) cells to DDP in vitro, which may be caused by CIP2A-induced AKT activity inhibition. Notably, CIP2A overexpression could significantly decrease the sensitivities of SKOV3 cells to cisplatin, which might be ascribed to CIP2A-induced activation of the AKT pathway.Taken together, the results suggest that CIP2A contributes to cisplatin resistance in OC. Thus, CIP2A is a potential therapeutic target for OC.