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Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells
Epithelial ovarian cancer is most lethal in female reproductive carcinomas owing to the high chemoresistance and metastasis, so more efficient therapeutic agents are terribly needed. A propadiene compound: 1-phenylpropadienyl phosphine oxide (PHPO), was employed to test the chemotherapeutic efficacy...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302979/ https://www.ncbi.nlm.nih.gov/pubmed/27494891 http://dx.doi.org/10.18632/oncotarget.11012 |
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author | Li, Shuqing Yang, Lina Wang, Jingshu Liang, Fan Chang, Bin Gu, Huafen Wang, Honglin Yang, Gong Chen, Yaping |
author_facet | Li, Shuqing Yang, Lina Wang, Jingshu Liang, Fan Chang, Bin Gu, Huafen Wang, Honglin Yang, Gong Chen, Yaping |
author_sort | Li, Shuqing |
collection | PubMed |
description | Epithelial ovarian cancer is most lethal in female reproductive carcinomas owing to the high chemoresistance and metastasis, so more efficient therapeutic agents are terribly needed. A propadiene compound: 1-phenylpropadienyl phosphine oxide (PHPO), was employed to test the chemotherapeutic efficacy against ovarian cancer cell lines. MTT assay showed that PHPO displayed a much lower IC50 than cisplatin and paclitaxel, while combination treatment of cells with PHPO + cisplatin induced more apoptosis than with PHPO + paclitaxel or with cisplatin + paclitaxel (p < 0.05). Animal assays demonstrated that subcutaneous tumor growth was highly inhibited by PHPO + cisplatin, compared with that inhibited by PHPO or by cisplatin treatment alone, indicating PHPO and cisplatin may have synergistic effects against ovarian cancer growth. We also found that PHPO induced few side effects on animals, compared with cisplatin. Mechanistic studies suggested that treatment of cells with PHPO or with PHPO + cisplatin differentially inhibited the PI3K/Akt, MAPK and ATM/Chk2 pathways, which consequently suppressed the anti-apoptotic factors Bcl-xL, Bcl-2 and XIAP, but activated the pro-apoptotic factors Bad, Bax, p53, caspase 9, caspase 8, caspase 7 and PARP. Taken together, PHPO may induce cell apoptosis through multiple signal pathways, especially when used along with cisplatin. Therefore, PHPO may be explored as a prospective agent to effectively treat ovarian cancer. |
format | Online Article Text |
id | pubmed-5302979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53029792017-02-13 Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells Li, Shuqing Yang, Lina Wang, Jingshu Liang, Fan Chang, Bin Gu, Huafen Wang, Honglin Yang, Gong Chen, Yaping Oncotarget Research Paper Epithelial ovarian cancer is most lethal in female reproductive carcinomas owing to the high chemoresistance and metastasis, so more efficient therapeutic agents are terribly needed. A propadiene compound: 1-phenylpropadienyl phosphine oxide (PHPO), was employed to test the chemotherapeutic efficacy against ovarian cancer cell lines. MTT assay showed that PHPO displayed a much lower IC50 than cisplatin and paclitaxel, while combination treatment of cells with PHPO + cisplatin induced more apoptosis than with PHPO + paclitaxel or with cisplatin + paclitaxel (p < 0.05). Animal assays demonstrated that subcutaneous tumor growth was highly inhibited by PHPO + cisplatin, compared with that inhibited by PHPO or by cisplatin treatment alone, indicating PHPO and cisplatin may have synergistic effects against ovarian cancer growth. We also found that PHPO induced few side effects on animals, compared with cisplatin. Mechanistic studies suggested that treatment of cells with PHPO or with PHPO + cisplatin differentially inhibited the PI3K/Akt, MAPK and ATM/Chk2 pathways, which consequently suppressed the anti-apoptotic factors Bcl-xL, Bcl-2 and XIAP, but activated the pro-apoptotic factors Bad, Bax, p53, caspase 9, caspase 8, caspase 7 and PARP. Taken together, PHPO may induce cell apoptosis through multiple signal pathways, especially when used along with cisplatin. Therefore, PHPO may be explored as a prospective agent to effectively treat ovarian cancer. Impact Journals LLC 2016-08-02 /pmc/articles/PMC5302979/ /pubmed/27494891 http://dx.doi.org/10.18632/oncotarget.11012 Text en Copyright: © 2016 Li et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Li, Shuqing Yang, Lina Wang, Jingshu Liang, Fan Chang, Bin Gu, Huafen Wang, Honglin Yang, Gong Chen, Yaping Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells |
title | Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells |
title_full | Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells |
title_fullStr | Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells |
title_full_unstemmed | Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells |
title_short | Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells |
title_sort | analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302979/ https://www.ncbi.nlm.nih.gov/pubmed/27494891 http://dx.doi.org/10.18632/oncotarget.11012 |
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