Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer.
Androgen deprivation therapy has become the fist-line treatment of metastatic prostate cancer; however, progression to castrate resistance disease occurs in the majority of patients. Thus, there is an urgent need for improvements in therapy for castration-resistant prostate cancer. The aims of the p...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3954761?pdf=render |
| _version_ | 1811336120739299328 |
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| author | Sha Zhu Judith Apondi Oremo Sanqiang Li Minghui Zhen Yue Tang Ying Du |
| author_facet | Sha Zhu Judith Apondi Oremo Sanqiang Li Minghui Zhen Yue Tang Ying Du |
| author_sort | Sha Zhu |
| collection | DOAJ |
| description | Androgen deprivation therapy has become the fist-line treatment of metastatic prostate cancer; however, progression to castrate resistance disease occurs in the majority of patients. Thus, there is an urgent need for improvements in therapy for castration-resistant prostate cancer. The aims of the present study were to determine the efficacy somatostatin analogue octreotide (OCT) combined with a low dose of docetaxel (DTX) using castration resistant prostate cancer cells and to investigate the involved molecular mechanisms in vitro. The anti-proliferative and synergism potential effects were determined by MTT assay. Induction of apoptosis was analyzed employing annexing V and propidium iodide staining and flow cytometry. VEGFA, CASP9, CASP3 and ABCB1 gene expression was evaluated by RT-PCR and Q-RT-PCR analysis. OCT in combination with DTX treatments on DU145 cell migration was also evaluated. Investigation revealed that combined administration of DTX and OCT had significant, synergistically greater cytotoxicity than DTX or OCT treatment alone. The combination of the two drugs caused a more marked increase in apoptosis and resulted in greater suppression of invasive potential than either individual agent. There was obvious increase in caspase 3 expression in the OCT alone and two-drug combined treatment groups, however, VEGFA expression was markedly suppressed in them. These results support the conclusion that somatostatin analogues combined with docetaxel may enhance the chemotherapy efficacies through multiple mechanisms in castration-resistant PCa cell line. This work provides a preclinical rationale for the therapeutic strategies to improve the treatment in castrate resistance disease. |
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| id | doaj.art-0dfe6f511daa4827b667552e2c4c37a6 |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T17:34:47Z |
| publishDate | 2014-01-01 |
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| spelling | doaj.art-0dfe6f511daa4827b667552e2c4c37a62022-12-22T02:37:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9181710.1371/journal.pone.0091817Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer.Sha ZhuJudith Apondi OremoSanqiang LiMinghui ZhenYue TangYing DuAndrogen deprivation therapy has become the fist-line treatment of metastatic prostate cancer; however, progression to castrate resistance disease occurs in the majority of patients. Thus, there is an urgent need for improvements in therapy for castration-resistant prostate cancer. The aims of the present study were to determine the efficacy somatostatin analogue octreotide (OCT) combined with a low dose of docetaxel (DTX) using castration resistant prostate cancer cells and to investigate the involved molecular mechanisms in vitro. The anti-proliferative and synergism potential effects were determined by MTT assay. Induction of apoptosis was analyzed employing annexing V and propidium iodide staining and flow cytometry. VEGFA, CASP9, CASP3 and ABCB1 gene expression was evaluated by RT-PCR and Q-RT-PCR analysis. OCT in combination with DTX treatments on DU145 cell migration was also evaluated. Investigation revealed that combined administration of DTX and OCT had significant, synergistically greater cytotoxicity than DTX or OCT treatment alone. The combination of the two drugs caused a more marked increase in apoptosis and resulted in greater suppression of invasive potential than either individual agent. There was obvious increase in caspase 3 expression in the OCT alone and two-drug combined treatment groups, however, VEGFA expression was markedly suppressed in them. These results support the conclusion that somatostatin analogues combined with docetaxel may enhance the chemotherapy efficacies through multiple mechanisms in castration-resistant PCa cell line. This work provides a preclinical rationale for the therapeutic strategies to improve the treatment in castrate resistance disease.http://europepmc.org/articles/PMC3954761?pdf=render |
| spellingShingle | Sha Zhu Judith Apondi Oremo Sanqiang Li Minghui Zhen Yue Tang Ying Du Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer. PLoS ONE |
| title | Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer. |
| title_full | Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer. |
| title_fullStr | Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer. |
| title_full_unstemmed | Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer. |
| title_short | Synergistic antitumor activities of docetaxel and octreotide associated with apoptotic-upregulation in castration-resistant prostate cancer. |
| title_sort | synergistic antitumor activities of docetaxel and octreotide associated with apoptotic upregulation in castration resistant prostate cancer |
| url | http://europepmc.org/articles/PMC3954761?pdf=render |
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