{"id":377,"date":"2015-11-04T00:00:00","date_gmt":"2015-11-03T23:00:00","guid":{"rendered":"http:\/\/semmelweis.hu\/symposium\/psmb7-a-new-biomarker-of-doxorubicin-and-paclitaxel-chemoresistance\/"},"modified":"2015-11-06T13:30:53","modified_gmt":"2015-11-06T12:30:53","slug":"psmb7-a-new-biomarker-of-doxorubicin-and-paclitaxel-chemoresistance","status":"publish","type":"page","link":"https:\/\/semmelweis.hu\/symposium\/szimpozium-archiv\/symposium2009-semmelweis\/temak\/psmb7-a-new-biomarker-of-doxorubicin-and-paclitaxel-chemoresistance\/","title":{"rendered":"PSMB7, a New Biomarker of Doxorubicin and Paclitaxel Chemoresistance"},"content":{"rendered":"\n<p>Zsuzsanna MIH\u00c1LY1, Gy. MUNK\u00c1CSY1,<br \/> R. SCH\u00c4FER2, R. ABDUL-GHANI2, B. GY\u00d5RFFY1,3<\/p>\n<p><em>1MTA-SE Research Group for Pediatrics and Nephrology;<br \/> 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary<br \/> 2Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany<br \/> 3Semmelweis University, 2nd Department of Pediatrics, Budapest, Hungary<\/em><\/p>\n<p><em>Background<\/em>: Doxorubicin and paclitaxel are first line drugs in the<br \/> chemotherapy of urinary bladder cancer. The development of<br \/> chemoresistance to these chemicals results in the reduction of their<br \/> efficiency. The product of the gene PSMB7 is a component of the<br \/> proteasome \u03b2 subunit, so far its role has not been studied in resistance<br \/> to doxorubicin or paclitaxel. The gene has significantly overexpressed<br \/> in doxorubicin-resistant cell-lines therefore the option of<br \/> its role in the generation of resistance has been identified. Since<br \/> cell-lines indicated resistance to paclitaxel as well, tests have been<br \/> conducted with the use of both drugs. Our research aims were to examine whether RNAi silencing of the PSMB7 gene has an impact<br \/> on the chemoresistance of doxorubicin-resistant cell-lines.<br \/> Methods:We worked with MCF-7 cell-lines. The gene was silenced<br \/> by RNA interference, which was produced by self designed siRNA<br \/> oligos and siPORT NeoFX transfection reagent. The validation of<br \/> the RNA happened with RNeasy Mini kit, the gene expression was<br \/> measured by RT-PCR. The drug treatment took place 24 hours after<br \/> transfection. The cells were counted by CASY DT Cell Counter.<br \/> Experiments were carried out three times with both doxorubicin<br \/> and paclitaxel, and each well was measured three times in each<br \/> experiment.<\/p>\n<p><em>Results<\/em>: 79.8%\u00b113.3% of resistance cells survived after doxorubicin<br \/> treatment. Combined with gene silencing, only<br \/> 31.8%\u00b16.4% of the MCF-7-RAdr cells survived. The significance<br \/> between siRNA-treated and siRNA-untreated MCF-7-RAdr cells<br \/> after doxorubicin treatment was p &gt; 0.001. After doxorubicin<br \/> treatment, 48.3\u00b18.1% of sensitive cells survived. 72.4% of negative<br \/> control siRNA-treated cells survived. After combination of<br \/> paclitaxel treatment and gene silencing, 22.6\u00b14% of the MCF-7-<br \/> RAdr cells survived compared to siRNA-untreated cells, while<br \/> 43.8\u00b16% of sensitive cells survived. Relative cell vitality of siRNAtreated<br \/> and siRNA-untreated MCF-7-RAdr cells after paclitaxel<br \/> treatment differed significantly (p = 0.03).<\/p>\n<p><em>Discussion<\/em>: According to our findings, by reducing the overexpression<br \/> of the PSMB7 gene via gene silencing the resistant cell&#8217;s<br \/> chemoresistance significantly decreased. Consequently the doxorubicin-<br \/> and paclitaxel-therapy became more efficient. In order to<br \/> predict clinical significance gene expression should be measured in<br \/> tumor samples from therapy resistant patients.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Zsuzsanna MIH\u00c1LY1, Gy. MUNK\u00c1CSY1, R. SCH\u00c4FER2, R. ABDUL-GHANI2, B. GY\u00d5RFFY1,3 1MTA-SE Research Group for Pediatrics and Nephrology; 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary 2Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany 3Semmelweis University, 2nd Department of Pediatrics, Budapest, Hungary Background: Doxorubicin and paclitaxel are first line drugs in the chemotherapy of urinary bladder cancer. The development of &hellip;<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":323,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"categories":[],"tags":[],"class_list":["post-377","page","type-page","status-publish","hentry"],"acf":[],"_links":{"self":[{"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/pages\/377","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/comments?post=377"}],"version-history":[{"count":1,"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/pages\/377\/revisions"}],"predecessor-version":[{"id":403,"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/pages\/377\/revisions\/403"}],"up":[{"embeddable":true,"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/pages\/323"}],"wp:attachment":[{"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/media?parent=377"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/categories?post=377"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/semmelweis.hu\/symposium\/wp-json\/wp\/v2\/tags?post=377"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}