TRAIL信号通路在胃癌的研究现状

Review of Signal Pathway of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Gastric Carcinoma

目的介绍肿瘤坏死因子相关凋亡诱导配体(TRAIL)及其受体在胃癌的研究现状。方法检索PUB-MEDLINE和中国期刊全文数据库(CJFD),综述国内、外近年关于TRAIL及其受体在胃癌的相关研究文献。结果TRAIL在胃癌组织表达水平报道情况差异较大,但其与胃癌的分化程度和浸润、转移情况密切相关。其受体DR4及DR5在胃癌组织均表达阳性,而DcR1及DcR2在胃癌组织亦有表达阳性的报道。caspase-3、caspase-8和survivin对胃癌TRAIL信号通路有重要调节作用。5-氮-2′-杂脱氧胞苷、阿霉素、5-氟尿嘧啶、α-生育酚及X射线照射可协同增强TRAIL对胃癌细胞的凋亡诱导作用。结论胃癌可能适合TRAIL靶向治疗,但其作用机理较为复杂并受到多因素影响。尚有如何有效增强和调控TRAIL凋亡诱导作用及TRAIL有何潜在毒性等诸多问题亟待研究。

Objective To review the current researches about tumor necrosis factor-related apoptosis ligand （TRAIL） and its receptors in gastric carcinoma. Methods Relevant articles of researches on TRAIl. and its receptors in gastric carcinoma were searched in electronic databases of PUB-MEDLINE and Chinese Journal Fulltext Database. Results The reported TRAIl. expression level of gastric carcinoma was diverse, which was highly correla ted to the histological differentiation degree, serosa invasion and lymph node metastasis. Its receptors DR4 and DR5 were both positive in gastric carcinoma tissue, while some researches reported DcR1 and DcR2 were also positive expressed, caspase-3, -8 and survivin were the important factors for regulation of TRAIl. signal pathway. 5-Aza-CdR, doxorubicin, 5-fluorouracil, a-TOS and X-ray irradiation might enhance the TRAIL-induced apoptosis of gastric carcinoma cells. Conclusion Gastric carcinoma may be potentially sensitive to TRAIl. targeting therapy, but the mechanism of TRAIL-induced apoptosis is quite complex and is regulated by multi-factors. Up to now, there are still many issues to research further, such as how to efficiently enhance and regulate the TRAIL-induced apoptosis of gastric carcinoma, whether any potential toxicities existing, etc.