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This study aims to examine whether doxycycline, a tetracycline antibiotic, can inhibit the enhanced migration of\n                    <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                    2\u2010deficient cells, identify signalling pathways through which doxycycline works and to assess the effectiveness of combining doxycycline with rapamycin (mammalian target of rapamycin complex 1 inhibitor) in controlling cell migration, proliferation and wound closure.\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    \u2010positive and\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    \u2010negative mouse embryonic fibroblasts (\n                    <jats:styled-content style=\"fixed-case\">MEF<\/jats:styled-content>\n                    ), 323\u2010\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    \u2010positive and 323\u2010\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    \u2010null\n                    <jats:styled-content style=\"fixed-case\">MEF<\/jats:styled-content>\n                    and Eker rat uterine leiomyoma (\n                    <jats:styled-content style=\"fixed-case\">ELT<\/jats:styled-content>\n                    3) cells were treated with doxycycline or rapamycin alone, or in combination. Migration, wound closure and proliferation were assessed using a transwell migration assay, time\u2010lapse microscopy and manual cell counts respectively. RhoA\u2010\n                    <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>\n                    ase activity, phosphorylation of p70S6 kinase (p70S6K) and focal adhesion kinase (\n                    <jats:styled-content style=\"fixed-case\">FAK<\/jats:styled-content>\n                    ) in\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    \u2010negative\n                    <jats:styled-content style=\"fixed-case\">MEF<\/jats:styled-content>\n                    treated with doxycycline were examined using ELISA and immunoblotting techniques. The enhanced migration of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    \u2010null cells was reduced by doxycycline at concentrations as low as 20\u00a0pM, while the rate of wound closure was reduced at 2\u201359\u00a0\u03bcM. Doxycycline decreased RhoA\u2010\n                    <jats:styled-content style=\"fixed-case\">GTP<\/jats:styled-content>\n                    ase activity and phosphorylation of\n                    <jats:styled-content style=\"fixed-case\">FAK<\/jats:styled-content>\n                    in these cells but had no effect on the phosphorylation of p70S6K,\n                    <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n                    1\/2 or\n                    <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>\n                    . Combining doxycycline with rapamycin significantly reduced the rate of wound closure at lower concentrations than achieved with either drug alone. This study shows that doxycycline inhibits\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                      2\n                    <\/jats:italic>\n                    \u2010null cell migration. Thus doxycycline has potential as an anti\u2010migratory agent in the treatment of diseases with\n                    <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>\n                    2 dysfunction.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.12593","type":"journal-article","created":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T05:58:05Z","timestamp":1439877485000},"page":"2633-2646","source":"Crossref","is-referenced-by-count":8,"title":["Doxycycline reduces the migration of tuberous sclerosis complex\u20102 null cells \u2010 effects on RhoA\u2010\n                    <scp>GTP<\/scp>\n                    ase and focal adhesion kinase"],"prefix":"10.1111","volume":"19","author":[{"given":"Ho Yin","family":"Ng","sequence":"first","affiliation":[{"name":"Sydney Medical School Discipline of Pharmacology University of Sydney Sydney NSW Australia"},{"name":"Cell Biology Group Woolcock Institute of Medical Research Sydney NSW 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