Cargando…
VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein
Lymphatic metastasis is a poor prognostic factor in ovarian cancer, which correlates to the majority of cancer deaths. Matrix protein (MP) of vesicular stomatitis virus (VSV) exhibits potent antitumor and antiangiogenic activities through inducing apoptosis and inhibiting angiogenesis. In this study...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902071/ https://www.ncbi.nlm.nih.gov/pubmed/27211072 http://dx.doi.org/10.3892/ijo.2016.3527 |
_version_ | 1782436927302008832 |
---|---|
author | QI, XIAORONG DU, LICHENG CHEN, XIANCHENG CHEN, LIJUAN YI, TAO CHEN, XIANG WEN, YANJUN WEI, YUQUAN ZHAO, XIA |
author_facet | QI, XIAORONG DU, LICHENG CHEN, XIANCHENG CHEN, LIJUAN YI, TAO CHEN, XIANG WEN, YANJUN WEI, YUQUAN ZHAO, XIA |
author_sort | QI, XIAORONG |
collection | PubMed |
description | Lymphatic metastasis is a poor prognostic factor in ovarian cancer, which correlates to the majority of cancer deaths. Matrix protein (MP) of vesicular stomatitis virus (VSV) exhibits potent antitumor and antiangiogenic activities through inducing apoptosis and inhibiting angiogenesis. In this study, the antitumor and antimetastatic effects of MP were further investigated. Wild-type SKOV3 (WT-SK) cells were successfully transfected with empty vector pcDNA3.1 plasmid, or pcDNA3.1-VEGF-D recombinant plasmid to construct cell lines named EV-SK, and VEGFD-SK, respectively. Inhibition of VEGFD-SK cell migration and invasion was detected by Transwell and wound healing assay. Then, lymphogenous metastatic model of ovarian cancer was established by injecting VEGFD-SK cells subcutaneously into the left hindlimb claw pad of nude mice. The inducted apoptotic effect of MP on VEGFD-SK cells were assessed by flow analysis and Hoechst-33258 staining, respectively, in vitro. The in vivo antitumor and antiangiogenic activities of MP gene were evaluated with lymphogenous metastatic model of ovarian cancer. Tumor volume and lymphatic metastasis rates were measured. Lymphatic vessels were delineated using Evan's blue and LYVE-1 staining. Expression of VEGF-D and MMP-2 were evaluated by immunostaining. Apoptosis of tumor cells was analyzed by Hoechst-33258 staining. Mice bearing VEGFD-SK tumor cells displayed more rapid tumorigenesis, higher lymphogenous metastatic tendency and increased lymphatic vessel density compared with the mice bearing WT-SK or EV-SK cells. However, VEGF-D-enhanced metastasis was evidently reversed by MP. MP significantly reduced the invasion of VEGFD-SK cells, tumor volume, lymphatic metastasis rates and lymphatic vessel density compared with control groups (P<0.05), accompanied with down-expression of VEGF-D and MMP-2 and increased apoptosis. Our data indicate that MP has strong antitumor and antimetastatic abilities, and it may be a promising therapeutic strategy against the lymphatic metastasis of human ovarian cancer. |
format | Online Article Text |
id | pubmed-4902071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-49020712016-06-24 VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein QI, XIAORONG DU, LICHENG CHEN, XIANCHENG CHEN, LIJUAN YI, TAO CHEN, XIANG WEN, YANJUN WEI, YUQUAN ZHAO, XIA Int J Oncol Articles Lymphatic metastasis is a poor prognostic factor in ovarian cancer, which correlates to the majority of cancer deaths. Matrix protein (MP) of vesicular stomatitis virus (VSV) exhibits potent antitumor and antiangiogenic activities through inducing apoptosis and inhibiting angiogenesis. In this study, the antitumor and antimetastatic effects of MP were further investigated. Wild-type SKOV3 (WT-SK) cells were successfully transfected with empty vector pcDNA3.1 plasmid, or pcDNA3.1-VEGF-D recombinant plasmid to construct cell lines named EV-SK, and VEGFD-SK, respectively. Inhibition of VEGFD-SK cell migration and invasion was detected by Transwell and wound healing assay. Then, lymphogenous metastatic model of ovarian cancer was established by injecting VEGFD-SK cells subcutaneously into the left hindlimb claw pad of nude mice. The inducted apoptotic effect of MP on VEGFD-SK cells were assessed by flow analysis and Hoechst-33258 staining, respectively, in vitro. The in vivo antitumor and antiangiogenic activities of MP gene were evaluated with lymphogenous metastatic model of ovarian cancer. Tumor volume and lymphatic metastasis rates were measured. Lymphatic vessels were delineated using Evan's blue and LYVE-1 staining. Expression of VEGF-D and MMP-2 were evaluated by immunostaining. Apoptosis of tumor cells was analyzed by Hoechst-33258 staining. Mice bearing VEGFD-SK tumor cells displayed more rapid tumorigenesis, higher lymphogenous metastatic tendency and increased lymphatic vessel density compared with the mice bearing WT-SK or EV-SK cells. However, VEGF-D-enhanced metastasis was evidently reversed by MP. MP significantly reduced the invasion of VEGFD-SK cells, tumor volume, lymphatic metastasis rates and lymphatic vessel density compared with control groups (P<0.05), accompanied with down-expression of VEGF-D and MMP-2 and increased apoptosis. Our data indicate that MP has strong antitumor and antimetastatic abilities, and it may be a promising therapeutic strategy against the lymphatic metastasis of human ovarian cancer. D.A. Spandidos 2016-05-17 /pmc/articles/PMC4902071/ /pubmed/27211072 http://dx.doi.org/10.3892/ijo.2016.3527 Text en Copyright: © Qi et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles QI, XIAORONG DU, LICHENG CHEN, XIANCHENG CHEN, LIJUAN YI, TAO CHEN, XIANG WEN, YANJUN WEI, YUQUAN ZHAO, XIA VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein |
title | VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein |
title_full | VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein |
title_fullStr | VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein |
title_full_unstemmed | VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein |
title_short | VEGF-D-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein |
title_sort | vegf-d-enhanced lymph node metastasis of ovarian cancer is reversed by vesicular stomatitis virus matrix protein |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902071/ https://www.ncbi.nlm.nih.gov/pubmed/27211072 http://dx.doi.org/10.3892/ijo.2016.3527 |
work_keys_str_mv | AT qixiaorong vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein AT dulicheng vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein AT chenxiancheng vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein AT chenlijuan vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein AT yitao vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein AT chenxiang vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein AT wenyanjun vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein AT weiyuquan vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein AT zhaoxia vegfdenhancedlymphnodemetastasisofovariancancerisreversedbyvesicularstomatitisvirusmatrixprotein |