| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
Synthetic lethality has attracted considerable attention as a novel strategy for the treatment of cancer. To explore RNA interference (RNAi) cancer therapy based on synthetic lethality, poly [ADP-ribose] polymerase 1 (PARP1) gene in human breast cancer cells lacking phosphatase and tensin homolog deleted from chromosome 10 (PTEN) was silenced by small interfering RNA targeting PARP1 (siPARP1). For the efficient delivery of siPARP1 to cancer cells, dicetylphosphate-tetraethylenepentamine-based polycation liposomes (TEPA-PCL) were prepared. Treatment with siPARP1 formulated in TEPA-PCL (siPARP1/TEPA-PCL) selectively induced DNA damage and cytocidal effects in PTEN-null cells, but not in PTEN-positive cells. These results indicate that PARP1 knockdown using siPARP1/TEPA-PCL is likely to be an effective strategy to achieve synthetic lethality against PTEN-null cancer.
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