Department of Orthopaedic Surgery, Mass General Hospital for Children, Pediatric Orthopaedic Laboratory for Tissue Engineering, Harvard Medical School, Boston, USA.
Int J Oral Sci. 2009 Jun;1(2):81-9. doi: 10.4248/ijos.08025.
To investigate the effect of DAPT (gamma-secretase inhibitor) on the growth of human tongue carcinoma cells and to determine the molecular mechanism to enable the potential application of DAPT to the treatment of tongue carcinoma.
Human tongue carcinoma Tca8113 cells were cultured with DAPT. Cell growth was determined using Indigotic Reduction method. The cell cycle and apoptosis were analyzed by flow cytometry. Real-time PCR and Immuno-Fluorescence (IF) were employed to determine the intracellular expression levels.
DAPT inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0-G1 cell cycle arrest and apoptosis. The mRNA levels of Hairy/Enhancer of Split-1 (Hes-1), a target of Notch activation, were reduced by DAPT in a dose-dependent manner. Coincident with this observation, DAPT induced a dose-dependent promotion of constitutive Caspase-3 in Tca8113 cells.
DAPT may have a therapeutic value for human tongue carcinoma. Moreover, the effects of DAPT in tumor inhibition may arise partly via the modulation of Notch-1 and Caspase-3.
研究 DAPT(γ-分泌酶抑制剂)对人舌癌细胞生长的影响,并确定其分子机制,以期将 DAPT 应用于舌癌的治疗。
用 DAPT 培养人舌癌细胞 Tca8113。采用靛红还原法检测细胞生长情况。采用流式细胞术分析细胞周期和凋亡。实时 PCR 和免疫荧光(IF)检测细胞内表达水平。
DAPT 通过诱导 G0-G1 细胞周期阻滞和凋亡抑制人舌癌细胞 Tca8113 的生长。DAPT 呈剂量依赖性降低 Notch 激活的靶基因 Hairy/Enhancer of Split-1(Hes-1)的 mRNA 水平。与此观察结果一致,DAPT 诱导 Tca8113 细胞中 Caspase-3 的组成性激活呈剂量依赖性增加。
DAPT 可能对人舌癌具有治疗价值。此外,DAPT 在肿瘤抑制中的作用可能部分是通过调节 Notch-1 和 Caspase-3 产生的。