Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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Research Abstract |
Lactoferrin (Lfn) show multi biological function including host defense against not only bacteria and virus but also malignant neoplasm. We previously reported that Lfn peptides (Lfn-p), produced by acid-pepsin hydrolysis of Lfn, induced apaptosis through JNK activation in human oral squamous cell carcinoma cell lines, SAS. (Sakai T et al., J Pharmacol Sci 98,2005) In contrast, we found that Lf-p-induced phospholipase D (PLD) activation in other squamous cell carcinoma cell line, HSC-4, survived in Lf-p-treatment. In the present study, we examined the effect of knockdown of endogenous PLD by small interference RNA (siRNA) on survival signaling activated with Lfn-p in HSC-4 cells. Both PLD1 and 2 were expressed in the cells. The reduction of expression level of PLD1, not PLD2, by siRNA transfection suppressed Lfn-p-induced PLD activity. Lfn-p-induced Akt phosphorylation, well-known survival signaling were also suppressed with PLD activity. Furthermore, JNK phosphorylaiton accompanied by Lfn-p-induced apoptosis in HSC-4 cells was increased in PLD1 knockdown cells. These results suggested that PLD1 was involved in cell survival through PI3K/Akt /JNK pathway in HSC-4 cells.
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