| Project/Area Number |
23800042
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Clinical oncology
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 遺伝子治療 / REIC / BiP/GRP78 / 小胞体ストレス / REIC/Dkk-3 / 前立腺がん / Bip/GRP78 |
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| Research Abstract |
We analyzed the synergistic effect of Bip/GRP78 inhibitors on the Ad-REIC treatment against prostate cancer. The optimal condition for the synergistic effect of Epigallocatechin gallate and 17-AAG to induce prostate cancer cells apoptosis under Ad-REIC treatment was not found, because these inhibitors induced apoptotic cell death by themselves. The new method to get more specific inhibition of Bip/GRP78 was needed. On the other hand, we investigated the new strategy to overcome the resistance of Ad-REIC or chemotherapeutic drugs. Significant cell growth inhibition was observed when the resistant bladder cancer cells, T24 and J82, were treated with Ad-REIC in a condition of floating cells. The adriamycin-resistantKK47 bladder cancer cell line (KK47/ADM), which also presents multiple drug resistance, showed induction of apoptosis with Ad-REIC at 100 MOI. The Ad-REIC treatment also induced down-regulation of P-glycoprotein in KK47/ADM and restored the sensitivity to Adriamycin. We originally constructed the plasmid vector that overexpressed the intracellular active domain of IRE1, which was regarded as one of ER stress sensors. Transfection with these vectors into prostate cancer cell line PC3 induced apoptotic cell death. These results suggested manipulation of ER stress would enhance the Ad-REIC treatment against prostate cancer.
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