Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice
<p>Abstract</p> <p>Background</p> <p>Signal transducer and activator of transcription 3 (STAT3) is usually constitutively activated in a variety of malignancies. Therefore, STAT3 may be a promising target for treatment of tumor cells. To explore the possibility of a dou...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2007-08-01
|
| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/7/149 |
| _version_ | 1818050348586106880 |
|---|---|
| author | Wei Haiming Wang Lihua Zhang Jian Zhang Xulong Tian Zhigang |
| author_facet | Wei Haiming Wang Lihua Zhang Jian Zhang Xulong Tian Zhigang |
| author_sort | Wei Haiming |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Signal transducer and activator of transcription 3 (STAT3) is usually constitutively activated in a variety of malignancies. Therefore, STAT3 may be a promising target for treatment of tumor cells. To explore the possibility of a double-stranded decoy oligodeoxynucleotide (ODN) targeted blocking STAT3 over-activated tumor cells, we, here, evaluate the efficacy of STAT3 decoy ODN on human lung cancer cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>A STAT3 decoy ODN was transfected into A549 lung cancer cell line <it>in vitro </it>by using lipofectamine. The flow cytometry and fluorescent microscopy were used to detect the transfection efficiency and the sub-cellular localization of STAT3 decoy ODN in A549 cells. Cell proliferation was determined by counting cell numbers and [<sup>3</sup>H]-thymidine uptake. Cell apoptosis was examined with Annexin V and propidum iodide by flow cytometry. The expression levels of STAT3 target genes were identified by RT-PCR and immunoblot. For <it>in vivo </it>experiment, A549 lung carcinoma-nude mice xenograft was used as a model to examine the effect of the STAT3 decoy by intratumoral injection. At the end of treatment, TUNEL and immunohistochemistry were used to examine the apoptosis and the expression levels of bcl-xl and cyclin D1 in tumor tissues.</p> <p>Results</p> <p>STAT3 decoy ODN was effectively transfected into A549 lung cancer cells and mainly located in nucleus. STAT3-decoy ODN significantly induced apoptosis and reduced [<sup>3</sup>H]-thymidine incorporation of A549 cells as well as down-regulated STAT3-target genes <it>in vitro</it>. STAT3 decoy ODN also dramatically inhibited the lung tumor growth in xenografted nude mice and decreased gene expression of bcl-xl and cyclin D1.</p> <p>Conclusion</p> <p>STAT3 decoy ODN significantly suppressed lung cancer cells <it>in vitro </it>and <it>in vivo</it>, indicating that STAT3 decoy ODN may be a potential therapeutic approach for treatment of lung cancer.</p> |
| first_indexed | 2024-12-10T10:52:03Z |
| format | Article |
| id | doaj.art-f6b6a77fe0d645d1993e31dbf5ead130 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-10T10:52:03Z |
| publishDate | 2007-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-f6b6a77fe0d645d1993e31dbf5ead1302022-12-22T01:51:58ZengBMCBMC Cancer1471-24072007-08-017114910.1186/1471-2407-7-149Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft miceWei HaimingWang LihuaZhang JianZhang XulongTian Zhigang<p>Abstract</p> <p>Background</p> <p>Signal transducer and activator of transcription 3 (STAT3) is usually constitutively activated in a variety of malignancies. Therefore, STAT3 may be a promising target for treatment of tumor cells. To explore the possibility of a double-stranded decoy oligodeoxynucleotide (ODN) targeted blocking STAT3 over-activated tumor cells, we, here, evaluate the efficacy of STAT3 decoy ODN on human lung cancer cells <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p>A STAT3 decoy ODN was transfected into A549 lung cancer cell line <it>in vitro </it>by using lipofectamine. The flow cytometry and fluorescent microscopy were used to detect the transfection efficiency and the sub-cellular localization of STAT3 decoy ODN in A549 cells. Cell proliferation was determined by counting cell numbers and [<sup>3</sup>H]-thymidine uptake. Cell apoptosis was examined with Annexin V and propidum iodide by flow cytometry. The expression levels of STAT3 target genes were identified by RT-PCR and immunoblot. For <it>in vivo </it>experiment, A549 lung carcinoma-nude mice xenograft was used as a model to examine the effect of the STAT3 decoy by intratumoral injection. At the end of treatment, TUNEL and immunohistochemistry were used to examine the apoptosis and the expression levels of bcl-xl and cyclin D1 in tumor tissues.</p> <p>Results</p> <p>STAT3 decoy ODN was effectively transfected into A549 lung cancer cells and mainly located in nucleus. STAT3-decoy ODN significantly induced apoptosis and reduced [<sup>3</sup>H]-thymidine incorporation of A549 cells as well as down-regulated STAT3-target genes <it>in vitro</it>. STAT3 decoy ODN also dramatically inhibited the lung tumor growth in xenografted nude mice and decreased gene expression of bcl-xl and cyclin D1.</p> <p>Conclusion</p> <p>STAT3 decoy ODN significantly suppressed lung cancer cells <it>in vitro </it>and <it>in vivo</it>, indicating that STAT3 decoy ODN may be a potential therapeutic approach for treatment of lung cancer.</p>http://www.biomedcentral.com/1471-2407/7/149 |
| spellingShingle | Wei Haiming Wang Lihua Zhang Jian Zhang Xulong Tian Zhigang Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice BMC Cancer |
| title | Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice |
| title_full | Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice |
| title_fullStr | Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice |
| title_full_unstemmed | Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice |
| title_short | Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice |
| title_sort | therapeutic effects of stat3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice |
| url | http://www.biomedcentral.com/1471-2407/7/149 |
| work_keys_str_mv | AT weihaiming therapeuticeffectsofstat3decoyoligodeoxynucleotideonhumanlungcancerinxenograftmice AT wanglihua therapeuticeffectsofstat3decoyoligodeoxynucleotideonhumanlungcancerinxenograftmice AT zhangjian therapeuticeffectsofstat3decoyoligodeoxynucleotideonhumanlungcancerinxenograftmice AT zhangxulong therapeuticeffectsofstat3decoyoligodeoxynucleotideonhumanlungcancerinxenograftmice AT tianzhigang therapeuticeffectsofstat3decoyoligodeoxynucleotideonhumanlungcancerinxenograftmice |