Radiosensitization by inhibition of cell survival signal

通过抑制细胞存活信号实现放射增敏

基本信息

批准号：
18591388
负责人：
KUBOTA Nobuo
金额：
$ 2.57万
依托单位：
Ibaraki Prefectural University of Health Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591388/
关键词：
Rdiosensitization Sulforaphane pancreatic cell line apoptosis Apaf-1 生存シグナル放射線増感効果 apigenin Bcl-2 Apaf-1

项目摘要

Sulforaphane (SFN), an isothiocyanate present in broccoli, is one of the most promising chemopreventive agents. It inhibits cell proliferation and induces apoptosis in different tumor cell lines, suggesting that SFN might be useful as chemotherapeutic agent for cancer treatment. In this study, we investigated the radiosensitizing effect of SFN in two human pancreatic cancer cell lines, MIA PaCA-2 and PANC-1. Radiation survival curves obtained showed that SFN radiosensitized both cell lines, but potentiated X-ray sensitivity more in MIAPaCa-2 than PANC-1 cells. In addition, SFN radiosensitized MIA PaCA-2 cells to apoptosis, but not PANC-1. The results obtained indicates that SFN-mediated radiosensitization by inducing apoptosis in MIA PaCa-2 cells is not regulated by Bc1-2 and Bax. A combined treatment of SFN and X-rays resulted in a decrease in the level of XIAP in both cells. MIA PaCa-2 cells treated with SFN and X-rays exhibited a marked increase in protein level of Apaf-1, which is essential for activation of.caspase-9. These results indicate that Apaf-1 is an important role in SFN-induced radiosensization by inducing apoptosis. Thus, SFN appears to be a promising radiosensitizing agent for use against human carcinomas.

萝卜硫素（SFN）是西兰花中存在的一种异硫氰酸盐，是最有前途的化学预防剂之一。它在不同的肿瘤细胞系中抑制细胞增殖并诱导细胞凋亡，这表明 SFN 可能可用作癌症治疗的化疗剂。在这项研究中，我们研究了 SFN 对两种人类胰腺癌细胞系 MIA PaCA-2 和 PANC-1 的放射增敏作用。获得的辐射存活曲线表明，SFN 对两种细胞系均具有放射敏感性，但在 MIAPaCa-2 细胞中比 PANC-1 细胞更能增强 X 射线敏感性。此外，SFN 使 MIA PaCA-2 细胞对细胞凋亡敏感，但对 PANC-1 细胞不敏感。获得的结果表明，SFN 通过诱导 MIA PaCa-2 细胞凋亡而介导的放射增敏作用不受 Bc1-2 和 Bax 的调节。 SFN 和 X 射线联合治疗导致两种细胞中 XIAP 水平下降。用SFN和X射线处理的MIA PaCa-2细胞表现出Apaf-1蛋白水平显着增加，这对于激活caspase-9至关重要。这些结果表明 Apaf-1 通过诱导细胞凋亡在 SFN 诱导的放射增敏中发挥重要作用。因此，SFN 似乎是一种有前途的用于对抗人类癌症的放射增敏剂。