| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Research Abstract |
This study aimed to examine whether the toxicity of molecular target drugs for human keratinocytes was associated with inhibiting signal transducer and activator of transcription 3 (STAT3). We studied whether STAT3 activity affects molecular target drugs-induced cell growth inhibition in HaCaT cells by WST-8 assay. Stattic enhanced the cell-growth inhibitory and apoptotic effects of molecular target drugs. HaCaT cells transfected with constitutively- active STAT3 (STAT3C) were resistant to the molecular target drugs-induced cell growth inhibition. STAT3 activity decreased after short-term treatment with sorafenib and sunitinib in a dose-dependent manner and recovered after long-term treatment with molecular target drugs at low doses. Moreover, HaCaT cells transfected with STAT3C showed high expression of apoptosis suppressors, e.g. bcl-2 and survivin. Thus, STAT3 activation mediating apoptosis suppressors may be a key factor in molecular target drugs-induced keratinocyte cytotoxicity.
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