Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo
Microvesicles shed from cells carry constituents of the cell cytoplasm, including, of importance in multidrug resistance to cancer chemotherapy, drugs that the tumor cell attempts to efflux. To see whether such drugs could be used at lower concentrations with the same efficacy, it was first shown th...
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| 格式: | 文件 |
| 语言: | English |
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Nature Group Publishing
2015
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| 在线阅读: | https://repository.londonmet.ac.uk/1000/1/Sci%20Rep%202015.pdf |
| _version_ | 1825624704144113664 |
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| author | Jorfi, Samireh Ansa-Addo, Ephraim A. Kholia, Sharadkumar Rajnikant Stratton, Dan Valley, Shaunelle Lange, Sigrun Inal, Jameel |
| author_facet | Jorfi, Samireh Ansa-Addo, Ephraim A. Kholia, Sharadkumar Rajnikant Stratton, Dan Valley, Shaunelle Lange, Sigrun Inal, Jameel |
| author_sort | Jorfi, Samireh |
| collection | LMU |
| description | Microvesicles shed from cells carry constituents of the cell cytoplasm, including, of importance in multidrug resistance to cancer chemotherapy, drugs that the tumor cell attempts to efflux. To see whether such drugs could be used at lower concentrations with the same efficacy, it was first shown that microvesiculation of prostate cancer (PCa) cells, PC3, could be inhibited pharmacologically with calpeptin (calpain inhibitor) and by siRNA (CAPNS1). In cells treated with docetaxel (DTX), this inhibition resulted in a third-fold increase in intracellular concentrations of DTX. As a result, 20-fold lower concentrations of DTX (5 nM) could be used, in the presence of calpeptin (20 μM) inducing the same degree of apoptosis after 48 h in PC3 cells, as 100 nM of DTX alone. Inhibition of microvesiculation similarly improved combination chemotherapy (DTX and methotrexate). In a mouse xenograft model of PCa, DTX (0.1 mg/kg) together with calpeptin (10 mg/kg), administered i.p., significantly reduced tumor volumes compared to DTX alone (0.1 mg/kg) and brought about the same reductions in tumor growth as 10 mg/kg of DTX alone. As well as further reducing vascularization, it also increased apoptosis and reduced proliferation of PC3 cells in tumor xenografts. |
| first_indexed | 2024-07-09T03:45:45Z |
| format | Article |
| id | oai:repository.londonmet.ac.uk:1000 |
| institution | London Metropolitan University |
| language | English |
| last_indexed | 2024-07-09T03:45:45Z |
| publishDate | 2015 |
| publisher | Nature Group Publishing |
| record_format | eprints |
| spelling | oai:repository.londonmet.ac.uk:10002020-06-22T14:43:10Z https://repository.londonmet.ac.uk/1000/ Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo Jorfi, Samireh Ansa-Addo, Ephraim A. Kholia, Sharadkumar Rajnikant Stratton, Dan Valley, Shaunelle Lange, Sigrun Inal, Jameel 610 Medicine & health Microvesicles shed from cells carry constituents of the cell cytoplasm, including, of importance in multidrug resistance to cancer chemotherapy, drugs that the tumor cell attempts to efflux. To see whether such drugs could be used at lower concentrations with the same efficacy, it was first shown that microvesiculation of prostate cancer (PCa) cells, PC3, could be inhibited pharmacologically with calpeptin (calpain inhibitor) and by siRNA (CAPNS1). In cells treated with docetaxel (DTX), this inhibition resulted in a third-fold increase in intracellular concentrations of DTX. As a result, 20-fold lower concentrations of DTX (5 nM) could be used, in the presence of calpeptin (20 μM) inducing the same degree of apoptosis after 48 h in PC3 cells, as 100 nM of DTX alone. Inhibition of microvesiculation similarly improved combination chemotherapy (DTX and methotrexate). In a mouse xenograft model of PCa, DTX (0.1 mg/kg) together with calpeptin (10 mg/kg), administered i.p., significantly reduced tumor volumes compared to DTX alone (0.1 mg/kg) and brought about the same reductions in tumor growth as 10 mg/kg of DTX alone. As well as further reducing vascularization, it also increased apoptosis and reduced proliferation of PC3 cells in tumor xenografts. Nature Group Publishing 2015-08-25 Article PeerReviewed text en https://repository.londonmet.ac.uk/1000/1/Sci%20Rep%202015.pdf Jorfi, Samireh, Ansa-Addo, Ephraim A., Kholia, Sharadkumar Rajnikant, Stratton, Dan, Valley, Shaunelle, Lange, Sigrun and Inal, Jameel (2015) Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo. Scientific Reports. ISSN 2045-2322 10.1038/srep13006 10.1038/srep13006 |
| spellingShingle | 610 Medicine & health Jorfi, Samireh Ansa-Addo, Ephraim A. Kholia, Sharadkumar Rajnikant Stratton, Dan Valley, Shaunelle Lange, Sigrun Inal, Jameel Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo |
| title | Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo |
| title_full | Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo |
| title_fullStr | Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo |
| title_full_unstemmed | Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo |
| title_short | Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo |
| title_sort | inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo |
| topic | 610 Medicine & health |
| url | https://repository.londonmet.ac.uk/1000/1/Sci%20Rep%202015.pdf |
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