Possibility of new treatment modality by inhibition of anti-apoptotic molecule XIAP

深入研究肿瘤细胞凋亡机制中的分子间机制可能有助于肿瘤治疗新模式的发明。在本研究中，一种假定的抗细胞凋亡分子XIAP，被用来研究其在新的治疗方式中的表达和作用。短干扰(Si)RNA对XIAP和GT作用的设计和检测；先前的研究表明，对XIAP的抑制不足促使我们转而使用siRNA。将3个序列用于siRNA，并克隆到适合siRNA的载体中。三种siRNA中的一种最能抑制XIAP的表达。将该载体分别导入Caki-1或LNCaP，获得10~12个克隆，并对其功能进行了研究。XIAP的表达及其与C反应蛋白、白介素6和肿瘤坏死因子途径及GT的关系在肾癌患者中，X IAP的表达与血清C反应蛋白呈显著正相关。在培养的细胞系中，部分细胞分泌高滴度的IL-6和TNF-α，并频繁表达XIAP。这表明，XIAP表达本身和肿瘤坏死因子途径双重抑制的可能性使XIAP更完全地被抑制，从而更容易受到凋亡刺激的影响。进一步的检查正在进行中。

Detailed study of inter-molecular mechanism in apoptotic machinery of tumor cells may contribute to invention of new modality of cancer therapy. In the present study, a putative anti-apoptotic molecule, XIAP, was investigated in terms its expression and action for new modality of treatment. < design and examination of its action of short interference (si) RNA to XIAP> Previous study revealed insufficient inhibition of XIAP tempted us to use siRNA instead. Three sequences were used to siRNA and cloned into a plasmid vector good for siRNA. One of the three siRNA was most potent to knock down XIAP expression. <stable transfectant> Ten to twelve clones each were isolated from transfection of the vector to Caki-1 or LNCap, and under investigation of its function. <XIAP expression and its relation to CRP, interleukin (IL)-6 and tumor necrosis factor(TNF) pathway> Statistically significant correlation between XIAP expression and serum CRP was noticed in renal cell cancer patients. Among cultured cell lines, some of them secreted high titer of IL-6 and TNF-alpha, and frequently expressed XIAP. This indicates that possibility of double inhibition of XIAP expression itself and TNF pathway render more complete inhibition of XIAP leading to more susceptible to apoptotic stimuli. Further examination was being performed.