{"corpus_id":9330608,"paper_sha":null,"doi":"10.1186/1476-4598-8-28","arxiv_id":null,"pmid":19445670,"pmcid":"2689171","mag_id":2124112278,"dblp_id":null,"acl_id":null,"title":"siRNA-based targeting of antiapoptotic genes can reverse chemoresistance in P-glycoprotein expressing chondrosarcoma cells","year":2009,"publication_date":"2009-05-15","venue":"Molecular Cancer","journal":{"name":"Molecular Cancer","pages":"28 - 28","volume":"8"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":33,"citation_count":57,"influential_citation_count":3,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"ATP Binding Cassette Transporter, Subfamily B, Member 1","mj":false,"qs":[{"q":"biosynthesis","mj":true,"ui":"Q000096"}],"ui":"D020168"},{"d":"Antineoplastic Agents","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D000970"},{"d":"Apoptosis","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D017209"},{"d":"Bone Neoplasms","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D001859"},{"d":"Cell Line, Tumor","mj":false,"ui":"D045744"},{"d":"Chondrosarcoma","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D002813"},{"d":"Doxorubicin","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D004317"},{"d":"Drug Resistance, Neoplasm","mj":false,"qs":[{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D019008"},{"d":"Flow Cytometry","mj":false,"ui":"D005434"},{"d":"Gene Silencing","mj":false,"ui":"D020868"},{"d":"Genes, bcl-2","mj":false,"ui":"D019254"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Immunoblotting","mj":false,"ui":"D015151"},{"d":"RNA, Small Interfering","mj":false,"ui":"D034741"},{"d":"Reverse Transcriptase Polymerase Chain Reaction","mj":false,"ui":"D020133"},{"d":"X-Linked Inhibitor of Apoptosis Protein","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D051636"},{"d":"bcl-X Protein","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D051020"}],"chemicals":[{"n":"ATP Binding Cassette Transporter, Subfamily B, Member 1","ui":"D020168","reg":"0"},{"n":"Antineoplastic Agents","ui":"D000970","reg":"0"},{"n":"RNA, Small Interfering","ui":"D034741","reg":"0"},{"n":"X-Linked Inhibitor of Apoptosis Protein","ui":"D051636","reg":"0"},{"n":"bcl-X Protein","ui":"D051020","reg":"0"},{"n":"Doxorubicin","ui":"D004317","reg":"80168379AG"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/1476-4598-8-28","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/205d57c1211d4f4e95a425eb36f0da7fa1527d4b","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"BackgroundHigh expression of P-glycoprotein is one of the well-known mechanisms of chemoresistance in chondrosarcomas. However, the role of antiapoptotic proteins, a common mechanism responsible for chemoresistance in other tumors, has not been well studied in chondrosarcomas. We examined the importance of P-glycoprotein and antiapoptotic proteins in the chemoresistance to doxorubicin of two Grade II chondrosarcoma cell lines, JJ012 and SW1353.ResultsWe confirmed that both chondrosarcoma cell types expressed P-glycoprotein and antiapoptotic proteins (Bcl-2, Bcl-xL and XIAP). siRNA knockdown as well as pharmacologic inhibitors of cell survival proteins (Bcl-2, Bcl-xL and XIAP) enhanced apoptosis of chemoresistant chondrosarcoma cells by up to 5.5 fold at 0.1 μmol and 5.5 fold at 1 μmol doxorubicin. These chemosensitizing effects were comparable to those of P-glycoprotein inhibition by siRNA or pharmacologic inhibitor.ConclusionThese findings suggest that antiapoptotic proteins play a significant role in the chemoresistance of chondrosarcoma cells independent of P-glycoprotein. Based on the results, a new siRNA-based therapeutic strategy targeting antiapoptotic genes can be designed to overcome the chemoresistance of chondrosarcomas which is often conferred by P-glycoprotein.","claims":[{"public_id":"cl_199eed958e5ea91fdc71872d9c05b2dc","status":"active","text":"An siRNA-based therapeutic strategy targeting antiapoptotic genes can be designed to overcome chondrosarcoma chemoresistance.","confidence":0.9,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_199eed958e5ea91fdc71872d9c05b2dc"},{"public_id":"cl_1799d71fce202bee6d530af66bcce495","status":"active","text":"Antiapoptotic proteins play a significant role in chondrosarcoma chemoresistance independent of P-glycoprotein.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_1799d71fce202bee6d530af66bcce495"},{"public_id":"cl_fb2a728ae61d3291542a2a589e5b45a0","status":"active","text":"P-glycoprotein and the antiapoptotic proteins Bcl-2, Bcl-xL, and XIAP are expressed in the two Grade II chondrosarcoma cell lines JJ012 and SW1353.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_fb2a728ae61d3291542a2a589e5b45a0"},{"public_id":"cl_5d00ffd9f07ba72ecff374fa7acbdc85","status":"active","text":"The chemosensitizing effects of targeting antiapoptotic proteins are comparable to those of P-glycoprotein inhibition by siRNA or pharmacologic inhibitor.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_5d00ffd9f07ba72ecff374fa7acbdc85"},{"public_id":"cl_d42d6ff7c41e548b029bd3e1be43429c","status":"active","text":"siRNA knockdown or pharmacologic inhibition of Bcl-2, Bcl-xL, and XIAP enhances apoptosis of chemoresistant chondrosarcoma cells by up to 5.5 fold at 0.1 μmol and 5.5 fold at 1 μmol doxorubicin.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_d42d6ff7c41e548b029bd3e1be43429c"}],"concepts":[{"public_id":"co_164dccbf7455cdd5b67db3e0626bb6c0","status":"active","name":"P-glycoprotein","description":"A membrane transporter associated with drug efflux and used here as a chemoresistance-related target.","types":["protein"],"aliases":["P-gp"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_164dccbf7455cdd5b67db3e0626bb6c0"},{"public_id":"co_17dc2a53d9502a17bb02f6d99a30f2a6","status":"active","name":"antiapoptotic proteins","description":"Proteins that inhibit apoptosis and can promote cell survival under treatment stress.","types":["protein category"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_17dc2a53d9502a17bb02f6d99a30f2a6"},{"public_id":"co_1d350090d4b9de21567e6d73e482bcb1","status":"active","name":"siRNA knockdown","description":"Gene silencing using small interfering RNA to reduce expression of specific targets.","types":["method"],"aliases":["siRNA inhibition","RNA interference"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_1d350090d4b9de21567e6d73e482bcb1"},{"public_id":"co_4baa780fa455e2fa346a298f9e23423b","status":"active","name":"chemoresistant chondrosarcoma cells","description":"Chondrosarcoma cells that show reduced sensitivity to chemotherapy.","types":["cell population"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_4baa780fa455e2fa346a298f9e23423b"},{"public_id":"co_4bd477297d18e56d75eddb73cd6805c5","status":"active","name":"doxorubicin","description":"An anthracycline chemotherapeutic agent used here to induce and measure drug response.","types":["drug"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_4bd477297d18e56d75eddb73cd6805c5"},{"public_id":"co_52b56d20507f511b2bb069e63fde692f","status":"active","name":"siRNA-based therapeutic strategy","description":"A treatment strategy that uses siRNA to suppress disease-related gene expression.","types":["therapeutic strategy"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_52b56d20507f511b2bb069e63fde692f"},{"public_id":"co_5d277af0af2dec4b5d40981252cdceb2","status":"active","name":"Bcl-2, Bcl-xL and XIAP","description":"A set of antiapoptotic proteins examined as survival-related contributors to drug resistance.","types":["protein group"],"aliases":["Bcl-2","Bcl-xL","XIAP"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_5d277af0af2dec4b5d40981252cdceb2"},{"public_id":"co_6663b056ce20813244c31660b0b4d81f","status":"active","name":"antiapoptotic genes","description":"Genes encoding proteins that suppress apoptosis and support cell survival.","types":["gene set"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_6663b056ce20813244c31660b0b4d81f"},{"public_id":"co_a61d3f5d18257917f438a8597cdaf961","status":"active","name":"chemoresistance","description":"Reduced responsiveness of tumor cells to chemotherapeutic treatment.","types":["phenomenon"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_a61d3f5d18257917f438a8597cdaf961"},{"public_id":"co_d2d5bb29fec6590ed8adcbc0bdaa6af9","status":"active","name":"pharmacologic inhibitors of cell survival proteins","description":"Drugs used to inhibit proteins that promote cell survival and resistance to apoptosis.","types":["treatment approach"],"aliases":["pharmacologic inhibitor"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_d2d5bb29fec6590ed8adcbc0bdaa6af9"},{"public_id":"co_fd52b8dc85c84cc880db4aa89a514620","status":"active","name":"chondrosarcoma chemoresistance","description":"Drug resistance specifically associated with chondrosarcoma cells.","types":["condition"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_fd52b8dc85c84cc880db4aa89a514620"},{"public_id":"co_fe62cbe87663a4332c6cc8f13c8c7cb5","status":"active","name":"Grade II chondrosarcoma cell lines JJ012 and SW1353","description":"Two human grade II chondrosarcoma cell lines used to test chemoresistance mechanisms.","types":["cell line"],"aliases":["JJ012","SW1353"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_fe62cbe87663a4332c6cc8f13c8c7cb5"}],"external_ids":{"DOI":"10.1186/1476-4598-8-28","ArXiv":null,"PubMed":19445670,"PubMedCentral":"2689171","MAG":2124112278,"DBLP":null,"ACL":null},"open_access":{"is_open_access":true,"pdf_url":"https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/1476-4598-8-28","landing_url":"https://www.semanticscholar.org/paper/205d57c1211d4f4e95a425eb36f0da7fa1527d4b","source":"semantic_scholar","pdf_url_source":"semantic_scholar_open_access_pdf","license":"CCBY","status":"GOLD","reason":null},"reference_availability":{"status":"available","references_indexed":true,"full_text_available":false,"full_text_source":null,"count_basis":"semantic_scholar_metadata","extraction_status":"not_applicable","reason":null},"source":{"provider":"episteme2","base_corpus":"semantic_scholar_dump","freshness_mode":"unknown","basis":["semantic_scholar_metadata","postgres_metadata"],"limits":["paper metadata is based on indexed upstream scholarly datasets","claims and concepts are available only for extracted papers","absence of claims or concepts means no extracted graph data is available in this response"],"status":"available","degraded":false,"degraded_reasons":[],"diagnostics":{"status":"available","degraded":false,"degraded_reasons":[],"metadata_status":"available","graph_status":"available","abstract_status":"available"},"source_flags":5},"paper_id":630683,"paper_uid":"9e5cfca1-ad63-4cc7-ab78-9979cd82ce6a","canonical_identity":{"paper_id":630683,"paper_uid":"9e5cfca1-ad63-4cc7-ab78-9979cd82ce6a","identity_status":"available","lookup_basis":"semantic_scholar_external_id","compatibility_path":"corpus_id"},"url":"https://sah.borca.ai/papers/9330608"}