Effect of VTCN1 on progression and metastasis of ovarian carcinoma in vitro and vivo.

BACKGROUND AND PURPOSES Through reducing immune response, VTCN1 could promote carcinoma indirectly. However, the direct effect of VTCN1 on carcinoma was not studied clearly, especially on ovarian carcinoma. In this paper, we verified the potential effect and mechanism of VTCN1 on ovarian carcinoma. METHODS The influence of high or low VTCN1 expression on the viability of ovarian cancer was detected by CKK-8 and annexin V-PI kit. The orthotopicxenograft tumor model was performed to evaluate the effect of VTCN1 on the promotion of tumor in vivo. Western blot was used to verify the signaling pathways predicted by bioinformatics analysis. RESULTS Low expression of VTCN1 could inhibit the viability and metastasis of ovarian carcinoma directly in vitro and vivo; Information analysis demonstrated that cell cycle and JAK2/STAT were involved in the regulation of VTCN1. The CDK2/4 and CDC25C expression and phosphorylation of JAK2/STAT had a direct relationship with the reduction of VTCN1. CONCLUSIONS VTCN1 could affect the viability and metastasis of ovarian carcinoma by reducing the expression of CDK2/4 and CDC25C and phosphorylation of JAK2/STAT. It indicated that VTCN1 was a potential target for treating ovarian carcinoma.

[1]  Fa-Yu Liu,et al.  CCR7 Regulates Cell Migration and Invasion through JAK2/STAT3 in Metastatic Squamous Cell Carcinoma of the Head and Neck , 2014, BioMed research international.

[2]  O. Silvennoinen,et al.  The activity of JAK-STAT pathways in rheumatoid arthritis: constitutive activation of STAT3 correlates with interleukin 6 levels. , 2015, Rheumatology.

[3]  Gang Li,et al.  The costimulatory molecule B7-H4 promote tumor progression and cell proliferation through translocating into nucleus , 2013, Oncogene.

[4]  B. Seliger,et al.  B7-H4 Expression in Human Melanoma: Its Association with Patients' Survival and Antitumor Immune Response , 2011, Clinical Cancer Research.

[5]  C. Dong,et al.  B7S1, a novel B7 family member that negatively regulates T cell activation. , 2003, Immunity.

[6]  Y. Kwon,et al.  HSP90 inhibitor NVP-AUY922 enhances TRAIL-induced apoptosis by suppressing the JAK2-STAT3-Mcl-1 signal transduction pathway in colorectal cancer cells. , 2015, Cellular signalling.

[7]  K. Keyomarsi,et al.  Cyclin E deregulation impairs mitotic progression through premature activation of Cdc25C. , 2010, Cancer research.

[8]  Yibang Chen,et al.  Inhibition of the JAK/STAT pathway with ruxolitinib overcomes cisplatin resistance in non-small-cell lung cancer NSCLC , 2014, Apoptosis.

[9]  J. Cheville,et al.  Genomic Organization and Expression Analysis of B7-H4, an Immune Inhibitory Molecule of the B7 Family 1 , 2003, The Journal of Immunology.

[10]  J. Cheville,et al.  B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival , 2006, Proceedings of the National Academy of Sciences.

[11]  M. Mandai,et al.  Long-term survival in metastatic malignant struma ovarii treated with oral chemotherapy: A case report , 2014, Oncology letters.

[12]  Eun Hee Lee,et al.  Perimenopausal Ovarian Carcinoma Patient with Subclavian Node Metastasis Proven by Immunohistochemistry , 2014, Journal of menopausal medicine.

[13]  Dongxia Gao,et al.  Systematic Analysis of Immune Infiltrates in High-Grade Serous Ovarian Cancer Reveals CD20, FoxP3 and TIA-1 as Positive Prognostic Factors , 2009, PloS one.

[14]  S. Natsugoe,et al.  Expression of B7‐H4 in blood of patients with gastric cancer predicts tumor progression and prognosis , 2010, Journal of surgical oncology.

[15]  George Coukos,et al.  Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. , 2003, The New England journal of medicine.

[16]  Xiaoping Zhang,et al.  Lexatumumab (TRAIL-receptor 2 mAb) induces expression of DR5 and promotes apoptosis in primary and metastatic renal cell carcinoma in a mouse orthotopic model. , 2007, Cancer letters.

[17]  B. Pützer,et al.  Spliceosomal protein E regulates neoplastic cell growth by modulating expression of Cyclin E/CDK2 and G2/M checkpoint proteins , 2008, Journal of cellular and molecular medicine.

[18]  S. Paternot,et al.  The CDK4/CDK6 inhibitor PD0332991 paradoxically stabilizes activated cyclin D3-CDK4/6 complexes , 2014, Cell cycle.

[19]  Mingxiong Guo,et al.  miR-638 Regulates Differentiation and Proliferation in Leukemic Cells by Targeting Cyclin-dependent Kinase 2* , 2014, The Journal of Biological Chemistry.

[20]  A. Chakraborty,et al.  Zerumbone inhibits growth of hormone refractory prostate cancer cells by inhibiting JAK2/STAT3 pathway and increases paclitaxel sensitivity , 2015, Anti-cancer drugs.

[21]  J. Nesland,et al.  CD117 Expression in Fibroblasts-Like Stromal Cells Indicates Unfavorable Clinical Outcomes in Ovarian Carcinoma Patients , 2014, PloS one.

[22]  H. Chae,et al.  NF-Y binds to both G1- and G2-specific cyclin promoters; a possible role in linking CDK2/Cyclin A to CDK1/Cyclin B. , 2011, BMB reports.

[23]  Hong-zhao Li,et al.  Downregulation of FOXO3a Promotes Tumor Metastasis and Is Associated with Metastasis-Free Survival of Patients with Clear Cell Renal Cell Carcinoma , 2014, Clinical Cancer Research.

[24]  E. Reed,et al.  Improving breast cancer therapy with CDK4/6 inhibitors. , 2014, Clinical Breast Cancer.

[25]  A. Epstein,et al.  Immune Signatures of Murine and Human Cancers Reveal Unique Mechanisms of Tumor Escape and New Targets for Cancer Immunotherapy , 2007, Clinical Cancer Research.

[26]  B7-H4 enhances oncogenicity and inhibits apoptosis in pancreatic cancer cells , 2013, Cell and Tissue Research.