| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Outline of Final Research Achievements |
We induced a rapamycin-resistant clear cell carcinoma cell line (Caki-1-RapR). We showed that survivin gene expression was significantly up-regulated in Caki-1-RapR compared with that in its parent cells (Caki-1). Caki-1-RapR cells had significantly more invasion ability than Caki-1 cells in a Matrigel invasion assay and more migration ability in a wound-healing assay. In Caki-1-RapR cells, rapamycin did not up-regulate caspase-9 activity and did not induce apoptosis. In Caki-1-RapR cells, YM155(survivin inhibitor) significantly decreased survivin gene and protein expression levels and cell proliferation in a dose-dependent manner in vitro. In addition, YM155 treatment significantly reversed rapamycin resistance in Caki-1-RapR cells. In a nude mouse tumor xenograft model, YM155 significantly inhibited the growth of Caki-1-RapR tumor. In addition, YM155 significantly enhanced the antitumor effects of rapamycin in Caki-1-RapR tumor.
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