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作用机制，将有助于肿瘤治疗的新模式。在本研究中，一个假定的抗凋亡分子，XIAP，在其表达和新的治疗方式的行动进行了研究。以前的研究显示XIAP的抑制不足，这促使我们使用siRNA代替。将三个序列用于siRNA并克隆到适合siRNA的质粒载体中。三种siRNA中的一种最有效地敲低XIAP表达。<stable transfectant>从载体转染至Caki-1或LNCap中分离出10至12个克隆，并对其功能进行研究。XIAP的表达与CRP、IL-6、TNF通路的关系XIAP的表达与血清CRP之间存在显著相关性。在培养的细胞系中，其中一些分泌高滴度的IL-6和TNF-α，并频繁表达XIAP。这表明XIAP表达本身和TNF途径的双重抑制的可能性使得XIAP的抑制更完全，导致对凋亡刺激更敏感。正在进行进一步检查。

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.