The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer.
<h4>Background</h4>Detecting a new effective and hypotoxic anticancer drug is an emerging new strategy for cancer chemotherapy. Doxycycline (DC) is a kind of antibiotics but also inhibits tumorigenesis.<h4>Methods</h4>MTT and cell invasion assay, flow cytometry, western-blot...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089841&type=printable |
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| _version_ | 1850190370681389056 |
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| author | Wei Wu Li-Hua Yu Bei Ma Ming-Juan Xu |
| author_facet | Wei Wu Li-Hua Yu Bei Ma Ming-Juan Xu |
| author_sort | Wei Wu |
| collection | DOAJ |
| description | <h4>Background</h4>Detecting a new effective and hypotoxic anticancer drug is an emerging new strategy for cancer chemotherapy. Doxycycline (DC) is a kind of antibiotics but also inhibits tumorigenesis.<h4>Methods</h4>MTT and cell invasion assay, flow cytometry, western-blot analysis and nude mice were used to investigate the effects and underlying mechanisms of doxycycline on epithelial ovarian cancer cells.<h4>Results</h4>Doxycycline inhibited the proliferation and invasion of SKOV3 and SKOV3/DDP; induced moderate apoptosis of SKOV3/DDP. CXCR4 expression at both mRNA and protein levels was downregulated in both cell lines when treated with doxycycline. Akt and ERK1/2 were involved in doxycycline effect on cell proliferation of SKOV3 but not of SKOV3/DDP. Akt and EKR1/2 phosphorylation were activated by SDF-1α, which was then inhibited by doxycycline in SKOV3. Pro-caspase-3 expression was significantly higher in SKOV3 than that in SKOV3/DDP which was upregulated when treated with doxycycline. In vivo, doxycycline inhibited peritoneal tumor xenograft and decreased malignant ascites.<h4>Conclusion</h4>Doxycycline not only has an inhibitory effect on ovarian cancer, but also can increase sensitivity to cisplatin. SDF-1α/CXCR4-regulated Akt and ERK 1/2 activations are probably involved in the antitumor effect of doxycycline on SKOV3 cells, while upregulation of pro-caspase-3 may be the main mechanism involved in SKOV3/DDP cells. |
| format | Article |
| id | doaj-art-fee10e1eb0e14229a6adecb88761f271 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-fee10e1eb0e14229a6adecb88761f2712025-08-20T02:15:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e8984110.1371/journal.pone.0089841The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer.Wei WuLi-Hua YuBei MaMing-Juan Xu<h4>Background</h4>Detecting a new effective and hypotoxic anticancer drug is an emerging new strategy for cancer chemotherapy. Doxycycline (DC) is a kind of antibiotics but also inhibits tumorigenesis.<h4>Methods</h4>MTT and cell invasion assay, flow cytometry, western-blot analysis and nude mice were used to investigate the effects and underlying mechanisms of doxycycline on epithelial ovarian cancer cells.<h4>Results</h4>Doxycycline inhibited the proliferation and invasion of SKOV3 and SKOV3/DDP; induced moderate apoptosis of SKOV3/DDP. CXCR4 expression at both mRNA and protein levels was downregulated in both cell lines when treated with doxycycline. Akt and ERK1/2 were involved in doxycycline effect on cell proliferation of SKOV3 but not of SKOV3/DDP. Akt and EKR1/2 phosphorylation were activated by SDF-1α, which was then inhibited by doxycycline in SKOV3. Pro-caspase-3 expression was significantly higher in SKOV3 than that in SKOV3/DDP which was upregulated when treated with doxycycline. In vivo, doxycycline inhibited peritoneal tumor xenograft and decreased malignant ascites.<h4>Conclusion</h4>Doxycycline not only has an inhibitory effect on ovarian cancer, but also can increase sensitivity to cisplatin. SDF-1α/CXCR4-regulated Akt and ERK 1/2 activations are probably involved in the antitumor effect of doxycycline on SKOV3 cells, while upregulation of pro-caspase-3 may be the main mechanism involved in SKOV3/DDP cells.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089841&type=printable |
| spellingShingle | Wei Wu Li-Hua Yu Bei Ma Ming-Juan Xu The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer. PLoS ONE |
| title | The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer. |
| title_full | The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer. |
| title_fullStr | The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer. |
| title_full_unstemmed | The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer. |
| title_short | The inhibitory effect of doxycycline on cisplatin-sensitive and -resistant epithelial ovarian cancer. |
| title_sort | inhibitory effect of doxycycline on cisplatin sensitive and resistant epithelial ovarian cancer |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089841&type=printable |
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