LBH589 和 TRAIL 的低剂量联合使用可以克服结肠癌细胞系对 TRAIL 的耐药性。
Low-dose combinations of LBH589 and TRAIL can overcome TRAIL-resistance in colon cancer cell lines.
机构信息
Division of Hematology-Oncology, Soonchunhyang University Hospital Seoul, 22 Daesagwan-gil, Yongsan-gu, Seoul 140-743, Republic of Korea.
出版信息
Anticancer Res. 2011 Oct;31(10):3385-94.
BACKGROUND
Despite the considerable advances in the treatment of colorectal cancer, substantial changes in treatment strategies are required to overcome the problems of drug resistance and toxicity.
MATERIALS AND METHODS
Combinations of Pan-deacetylase inhibitor LBH589 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were studied in three colon cancer cell lines, HCT116, colo205, and HT29 (HCT116 and colo205 are TRAIL sensitive, whereas HT29 is TRAIL resistant).
RESULTS
It was found that TRAIL-induced cytotoxicity was enhanced by LBH589 cotreatment in the TRAIL-sensitive cell lines, and in the TRAIL-resistant HT29 cell line. The cytotoxicity of low-dose TRAIL plus LBH589 was found to be comparable to that of high-dose TRAIL plus LBH589. Additionally, TRAIL and LBH589 were significantly less toxic to normal UCB mononuclear cells than to the three colon cancer cell lines examined.
CONCLUSION
LBH589 enhances TRAIL-induced apoptosis in human colon cancer cell lines, especially those resistant to TRAIL-induced apoptosis.
背景
尽管在结直肠癌的治疗方面取得了相当大的进展，但仍需要对治疗策略进行重大改变，以克服耐药性和毒性问题。
材料和方法
在三种结肠癌细胞系（HCT116、colo205 和 HT29）中研究了泛脱乙酰酶抑制剂 LBH589 和肿瘤坏死因子相关凋亡诱导配体（TRAIL）的组合，其中 HCT116 和 colo205 对 TRAIL 敏感，而 HT29 对 TRAIL 耐药。
结果
发现 LBH589 共处理增强了 TRAIL 敏感细胞系中 TRAIL 诱导的细胞毒性，并且在 TRAIL 耐药的 HT29 细胞系中也是如此。发现低剂量 TRAIL 加 LBH589 的细胞毒性与高剂量 TRAIL 加 LBH589 的细胞毒性相当。此外，与所检查的三种结肠癌细胞系相比，TRAIL 和 LBH589 对正常 UCB 单核细胞的毒性明显较小。
结论
LBH589 增强了人结肠癌细胞系中 TRAIL 诱导的细胞凋亡，特别是对 TRAIL 诱导的细胞凋亡耐药的细胞系。
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