Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
J Cell Biochem. 2010 Aug 1;110(5):1073-81. doi: 10.1002/jcb.22619.
Approximately 25% of patients with colorectal cancer develop metastases to the liver, and surgery is currently the best treatment available. But there are several patients who are unresectable, and isolated hepatic perfusion (IHP) offers a different approach in helping to treat these patients. IHP is a method used for isolating the liver and delivering high doses of chemotherapeutic agents. The efficacy of IHP has been improved by combining hyperthermia not only with chemotherapeutics but with other deliverable agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study, we used human colorectal cancer CX-1 cells and treated them with hyperthermia and TRAIL, causing cytotoxicity. We were able to demonstrate that the numbers of live cells were significantly reduced with hyperthermia and 10 ng/ml of TRAIL combined. We also showed that the effect of hyperthermia on TRAIL in our studies was enhancement of the apoptotic pathway by the promotion of JNK and Bim(EL) activity as well as PARP cleavage. We have also used our CX-1 cells to generate tumors in Balb/c nude mice. With intratumoral injections of TRAIL combined with hyperthermia at 42 degrees C, we were able to show a delayed onset of tumor growth in our xenograft model.
大约 25%的结直肠癌患者会发生肝转移，目前手术是最有效的治疗方法。但仍有部分患者无法进行手术切除，而孤立性肝灌注（IHP）为这些患者提供了一种不同的治疗方法。IHP 是一种用于隔离肝脏并输送高剂量化疗药物的方法。通过将高温与化疗药物以及其他可输送的药物（如肿瘤坏死因子相关凋亡诱导配体（TRAIL））联合使用，提高了 IHP 的疗效。在这项研究中，我们使用人结直肠癌细胞 CX-1 并对其进行高温和 TRAIL 处理，导致细胞毒性。我们能够证明，与单独使用高温或 10ng/ml TRAIL 相比，联合使用时活细胞数量显著减少。我们还表明，在我们的研究中，高温对 TRAIL 的作用是通过促进 JNK 和 Bim(EL)活性以及 PARP 切割来增强凋亡途径。我们还使用 CX-1 细胞在 Balb/c 裸鼠中生成肿瘤。通过对肿瘤内注射 TRAIL 并联合 42°C 的高温处理，我们能够在异种移植模型中观察到肿瘤生长的延迟。
