Radiosensitization by inhibition of cell survival signal

萝卜硫素（SFN）是一种存在于花椰菜中的异硫氰酸酯，是最有前途的化学预防剂之一。SFN在不同的肿瘤细胞系中抑制细胞增殖并诱导细胞凋亡，表明SFN可能用作癌症治疗的化疗剂。在这项研究中，我们研究了SFN在两种人胰腺癌细胞系MIA PaCA-2和PANC-1中的放射增敏作用。放射存活曲线表明，SFN放射增敏两种细胞系，但增强X射线敏感性MIAPaCa-2比PANC-1细胞。此外，SFN放射增敏MIA PaCA-2细胞凋亡，但不是PANC-1。所获得的结果表明，SFN介导的放射增敏通过诱导MIA PaCa-2细胞中的凋亡不受Bcl-2和Bax的调节。SFN和X射线的联合治疗导致两种细胞中XIAP水平的降低。经SFN和X射线处理的MIA PaCa-2细胞表现出Apaf-1蛋白水平的显著增加，Apaf-1蛋白水平对于caspase-9的活化是必需的。这些结果表明Apaf-1通过诱导细胞凋亡在SFN诱导的放射增敏中起重要作用。因此，SFN似乎是一个有前途的放射增敏剂，用于对人类癌症。

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.