RNA interference-directed caveolin-1 knockdown sensitizes SN12CPM6 cells to doxorubicin-induced apoptosis and reduces lung metastasis
Human renal cell carcinoma (HRCC) is characterized by a high level of resistance to all treatment modalities. Therefore, the investigation of global gene expression in HRCC might help understand its biologic behavior and develop treatment strategies. Using cDNA microarray analysis, we initially comp...
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| Veröffentlicht in: | Tumor biology 2010-12, Vol.31 (6), p.643-650 |
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| creator | Park, Juwon Bae, Eunkyung Lee, Chansu Yoon, Sung-Soo Chae, Yang Seok Ahn, Kwang-Sung Won, Nam Hee |
| description | Human renal cell carcinoma (HRCC) is characterized by a high level of resistance to all treatment modalities. Therefore, the investigation of global gene expression in HRCC might help understand its biologic behavior and develop treatment strategies. Using cDNA microarray analysis, we initially compared gene expression profiles between HRCCs and adjacent normal tissues, and found that 87 were up-regulated and 127 genes were down-regulated. Next, a subset of genes, twofold differentially expressed, were validated by Northern blotting. Unexpectedly, caveolin-1, a gene reported to be a tumor suppressor gene, was found to be up-regulated in HRCC tissues. Expression level of caveolin-1 in SN12CPM6 (high metastatic clone) was higher than in SN12C (low metastatic clone), and SN12CPM6 was more resistant to doxorubicin (DXR) than SN12C. Caveolin-1 gene was slightly induced in surviving SN12C cells after DXR treatment. Furthermore, SN12CPM6-siCav1 cells, which were transfected with siRNA of cavelon-1 gene, were more sensitive to DXR, compared to SN12CPM6, but reduction of caveolin-1 gene expression did not affect tumor formation in subcapsule of kidney and lung metastasis. On the other hand, induction of caveolin-1 gene affected the production of lung metastasis under anti-cancer drug treatment: the incidence of pulmonary metastasis was significantly lower in SCID mice injected with SN12CPM6-siCav1 cells, and the number of pulmonary nodules decreased significantly (
p
= 0.0004). The above results together suggest that caveolin-1 may confer a growth advantage to cancer cells during DXR chemotherapy and surviving HRCC cells eventually might develop lung metastasis. |
| doi_str_mv | 10.1007/s13277-010-0081-1 |
| format | Article |
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p
= 0.0004). The above results together suggest that caveolin-1 may confer a growth advantage to cancer cells during DXR chemotherapy and surviving HRCC cells eventually might develop lung metastasis.</description><identifier>ISSN: 1010-4283</identifier><identifier>EISSN: 1423-0380</identifier><identifier>DOI: 10.1007/s13277-010-0081-1</identifier><identifier>PMID: 20820979</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Animals ; Antibiotics, Antineoplastic - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - pathology ; Caveolin 1 - genetics ; Caveolin 1 - metabolism ; Cell Line, Tumor ; Down-Regulation - drug effects ; Doxorubicin - pharmacology ; Gene expression ; Humans ; Kidney diseases ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - pathology ; Lung cancer ; Lung Neoplasms - prevention & control ; Lung Neoplasms - secondary ; Metastasis ; Mice ; Mice, Nude ; Mice, SCID ; Neoplasm Metastasis - prevention & control ; Research Article ; RNA Interference - physiology ; RNA, Small Interfering - genetics ; Transfection ; Transplantation, Heterologous ; Up-Regulation - drug effects</subject><ispartof>Tumor biology, 2010-12, Vol.31 (6), p.643-650</ispartof><rights>International Society of Oncology and BioMarkers (ISOBM) 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-e135cfe3c6bf19b962bb97b847c801f022b078284aaa1f3a1dcf5015224d75fd3</citedby><cites>FETCH-LOGICAL-c402t-e135cfe3c6bf19b962bb97b847c801f022b078284aaa1f3a1dcf5015224d75fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13277-010-0081-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13277-010-0081-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20820979$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Juwon</creatorcontrib><creatorcontrib>Bae, Eunkyung</creatorcontrib><creatorcontrib>Lee, Chansu</creatorcontrib><creatorcontrib>Yoon, Sung-Soo</creatorcontrib><creatorcontrib>Chae, Yang Seok</creatorcontrib><creatorcontrib>Ahn, Kwang-Sung</creatorcontrib><creatorcontrib>Won, Nam Hee</creatorcontrib><title>RNA interference-directed caveolin-1 knockdown sensitizes SN12CPM6 cells to doxorubicin-induced apoptosis and reduces lung metastasis</title><title>Tumor biology</title><addtitle>Tumor Biol</addtitle><addtitle>Tumour Biol</addtitle><description>Human renal cell carcinoma (HRCC) is characterized by a high level of resistance to all treatment modalities. Therefore, the investigation of global gene expression in HRCC might help understand its biologic behavior and develop treatment strategies. Using cDNA microarray analysis, we initially compared gene expression profiles between HRCCs and adjacent normal tissues, and found that 87 were up-regulated and 127 genes were down-regulated. Next, a subset of genes, twofold differentially expressed, were validated by Northern blotting. Unexpectedly, caveolin-1, a gene reported to be a tumor suppressor gene, was found to be up-regulated in HRCC tissues. Expression level of caveolin-1 in SN12CPM6 (high metastatic clone) was higher than in SN12C (low metastatic clone), and SN12CPM6 was more resistant to doxorubicin (DXR) than SN12C. Caveolin-1 gene was slightly induced in surviving SN12C cells after DXR treatment. Furthermore, SN12CPM6-siCav1 cells, which were transfected with siRNA of cavelon-1 gene, were more sensitive to DXR, compared to SN12CPM6, but reduction of caveolin-1 gene expression did not affect tumor formation in subcapsule of kidney and lung metastasis. On the other hand, induction of caveolin-1 gene affected the production of lung metastasis under anti-cancer drug treatment: the incidence of pulmonary metastasis was significantly lower in SCID mice injected with SN12CPM6-siCav1 cells, and the number of pulmonary nodules decreased significantly (
p
= 0.0004). The above results together suggest that caveolin-1 may confer a growth advantage to cancer cells during DXR chemotherapy and surviving HRCC cells eventually might develop lung metastasis.</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - pathology</subject><subject>Caveolin 1 - genetics</subject><subject>Caveolin 1 - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Down-Regulation - drug effects</subject><subject>Doxorubicin - pharmacology</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Kidney diseases</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - pathology</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - prevention & control</subject><subject>Lung Neoplasms - secondary</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Mice, SCID</subject><subject>Neoplasm Metastasis - prevention & control</subject><subject>Research Article</subject><subject>RNA Interference - physiology</subject><subject>RNA, Small Interfering - genetics</subject><subject>Transfection</subject><subject>Transplantation, Heterologous</subject><subject>Up-Regulation - drug effects</subject><issn>1010-4283</issn><issn>1423-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kUuLFTEQhRtRnHH0B7iR4MZVa1XStx_L4aKOMI7iYx3SSWXITN_kmuoeH3v_t2nuqCAIgYSq75yqcKrqMcJzBOheMCrZdTUg1AA91ninOsZGqhpUD3fLe-00sldH1QPmKwDcDEN7vzqS0EsYuuG4-vnh4lSEOFP2lClaql3IZGdywpobSlOINYrrmOy1S1-jYIoc5vCDWHy8QLl9_7YVlqaJxZyES99SXsZgiyhEt9jiYvZpPycOLEx0ItNaZTEt8VLsaDZcTuCH1T1vJqZHt_dJ9fnVy0_bs_r83es329Pz2jYg55pQbawnZdvR4zAOrRzHoRv7prM9oAcpR-h62TfGGPTKoLN-Uz4tZeO6jXfqpHp28N3n9GUhnvUu8Lq-iZQW1gM0Td-2qi3k03_Iq7TkWJbTZZxCqSQUCA-QzYk5k9f7HHYmf9cIek1IHxLSJQe9JqSxaJ7cGi_jjtwfxe9ICiAPAJdWvKT8d_L_XX8BMTOcvQ</recordid><startdate>20101201</startdate><enddate>20101201</enddate><creator>Park, Juwon</creator><creator>Bae, Eunkyung</creator><creator>Lee, Chansu</creator><creator>Yoon, Sung-Soo</creator><creator>Chae, Yang Seok</creator><creator>Ahn, Kwang-Sung</creator><creator>Won, Nam Hee</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7TM</scope></search><sort><creationdate>20101201</creationdate><title>RNA interference-directed caveolin-1 knockdown sensitizes SN12CPM6 cells to doxorubicin-induced apoptosis and reduces lung metastasis</title><author>Park, Juwon ; Bae, Eunkyung ; Lee, Chansu ; Yoon, Sung-Soo ; Chae, Yang Seok ; Ahn, Kwang-Sung ; Won, Nam Hee</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-e135cfe3c6bf19b962bb97b847c801f022b078284aaa1f3a1dcf5015224d75fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Carcinoma, Renal Cell - pathology</topic><topic>Caveolin 1 - genetics</topic><topic>Caveolin 1 - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Down-Regulation - drug effects</topic><topic>Doxorubicin - pharmacology</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Kidney diseases</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidney Neoplasms - pathology</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - prevention & control</topic><topic>Lung Neoplasms - secondary</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Mice, SCID</topic><topic>Neoplasm Metastasis - prevention & control</topic><topic>Research Article</topic><topic>RNA Interference - physiology</topic><topic>RNA, Small Interfering - genetics</topic><topic>Transfection</topic><topic>Transplantation, Heterologous</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Juwon</creatorcontrib><creatorcontrib>Bae, Eunkyung</creatorcontrib><creatorcontrib>Lee, Chansu</creatorcontrib><creatorcontrib>Yoon, Sung-Soo</creatorcontrib><creatorcontrib>Chae, Yang Seok</creatorcontrib><creatorcontrib>Ahn, Kwang-Sung</creatorcontrib><creatorcontrib>Won, Nam Hee</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Juwon</au><au>Bae, Eunkyung</au><au>Lee, Chansu</au><au>Yoon, Sung-Soo</au><au>Chae, Yang Seok</au><au>Ahn, Kwang-Sung</au><au>Won, Nam Hee</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RNA interference-directed caveolin-1 knockdown sensitizes SN12CPM6 cells to doxorubicin-induced apoptosis and reduces lung metastasis</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2010-12-01</date><risdate>2010</risdate><volume>31</volume><issue>6</issue><spage>643</spage><epage>650</epage><pages>643-650</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><abstract>Human renal cell carcinoma (HRCC) is characterized by a high level of resistance to all treatment modalities. Therefore, the investigation of global gene expression in HRCC might help understand its biologic behavior and develop treatment strategies. Using cDNA microarray analysis, we initially compared gene expression profiles between HRCCs and adjacent normal tissues, and found that 87 were up-regulated and 127 genes were down-regulated. Next, a subset of genes, twofold differentially expressed, were validated by Northern blotting. Unexpectedly, caveolin-1, a gene reported to be a tumor suppressor gene, was found to be up-regulated in HRCC tissues. Expression level of caveolin-1 in SN12CPM6 (high metastatic clone) was higher than in SN12C (low metastatic clone), and SN12CPM6 was more resistant to doxorubicin (DXR) than SN12C. Caveolin-1 gene was slightly induced in surviving SN12C cells after DXR treatment. Furthermore, SN12CPM6-siCav1 cells, which were transfected with siRNA of cavelon-1 gene, were more sensitive to DXR, compared to SN12CPM6, but reduction of caveolin-1 gene expression did not affect tumor formation in subcapsule of kidney and lung metastasis. On the other hand, induction of caveolin-1 gene affected the production of lung metastasis under anti-cancer drug treatment: the incidence of pulmonary metastasis was significantly lower in SCID mice injected with SN12CPM6-siCav1 cells, and the number of pulmonary nodules decreased significantly (
p
= 0.0004). The above results together suggest that caveolin-1 may confer a growth advantage to cancer cells during DXR chemotherapy and surviving HRCC cells eventually might develop lung metastasis.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>20820979</pmid><doi>10.1007/s13277-010-0081-1</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Tumor biology, 2010-12, Vol.31 (6), p.643-650 |
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| subjects | Animals Antibiotics, Antineoplastic - pharmacology Apoptosis Apoptosis - drug effects Biomedical and Life Sciences Biomedicine Cancer Research Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology Caveolin 1 - genetics Caveolin 1 - metabolism Cell Line, Tumor Down-Regulation - drug effects Doxorubicin - pharmacology Gene expression Humans Kidney diseases Kidney Neoplasms - metabolism Kidney Neoplasms - pathology Lung cancer Lung Neoplasms - prevention & control Lung Neoplasms - secondary Metastasis Mice Mice, Nude Mice, SCID Neoplasm Metastasis - prevention & control Research Article RNA Interference - physiology RNA, Small Interfering - genetics Transfection Transplantation, Heterologous Up-Regulation - drug effects |
| title | RNA interference-directed caveolin-1 knockdown sensitizes SN12CPM6 cells to doxorubicin-induced apoptosis and reduces lung metastasis |
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