| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Outline of Final Research Achievements |
Cetuximab is a recombinant human/mouse chimeric monoclonal antibody which competitively binds to epidermal growth factor receptor (EGFR) resulting in inhibition of cell growth, angiogenesis and invasion. Despite initial drug activity, some patients often have resistance against Cetuximab. The aim of this study is to discover the resistant mechanism and to detect a new drug, which overcomes the resistance. Microarray assay and real time PCR using 3 pairs of sensitive and resistant cells, which have been established by us, revealed that PLAUR gene may be a candidate resistant gene. Transformantion by PLAUR shRNA makes the resistant ability weaker. Via integrin β1 signal transduction pathway, overexpression of PLAUR gene upregulates cell growth resulting in acquire the resistance against Cetuximab. Resveratrol was detected as inhibitor of PLAUR gene and it was confirmed in vitro and in vivo that Resveratrol weakens the resistance against Cetuximab.
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