Kim Seong C, Park Sung-Soo, Lee Yong J
Department of Surgery and Pharmacology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
J Cell Biochem. 2008 Jul 1;104(4):1172-80. doi: 10.1002/jcb.21682.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL shows strong cytotoxicity to many cancer cells but minimal cytotoxicity to most normal cells. Interestingly, our recent studies have demonstrated that pretreatment with TRAIL induces acquired resistance to TRAIL (Song et al. 2007 J Biol Chem 282: 319). Acquired TRAIL resistance develops within 1 day and gradually decays within 5 days after TRAIL treatment. In our current study, we examined whether human colorectal carcinoma CX-1 cells with acquired TRAIL resistance are resistant to UV irradiation as well. CX-1 cells were treated with 200 ng/ml TRAIL for 6 h and incubated various times (0.25-5 days) and then challenged to UV irradiation. Unexpectedly, we observed an increase in apoptosis in acquired TRAIL resistant cells after UVC as well as UVB exposure. This was due to an increase in caspase activation which was mediated through cytochrome c release. These results suggest that cells with acquired TRAIL resistance are sensitive to UV irradiation.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）是肿瘤坏死因子超家族的一员。TRAIL对许多癌细胞具有很强的细胞毒性，但对大多数正常细胞的细胞毒性极小。有趣的是，我们最近的研究表明，用TRAIL预处理会诱导对TRAIL产生获得性抗性（Song等人，2007年，《生物化学杂志》282:319）。获得性TRAIL抗性在TRAIL处理后1天内产生，并在5天内逐渐消退。在我们目前的研究中，我们研究了具有获得性TRAIL抗性的人结肠癌细胞CX-1是否也对紫外线照射具有抗性。将CX-1细胞用200 ng/ml TRAIL处理6小时，并孵育不同时间（0.25 - 5天），然后进行紫外线照射。出乎意料的是，我们观察到在UVC以及UVB照射后，获得性TRAIL抗性细胞中的凋亡增加。这是由于通过细胞色素c释放介导的半胱天冬酶激活增加所致。这些结果表明，具有获得性TRAIL抗性的细胞对紫外线照射敏感。
