PIK3CA基因通过编码P110激活PI3K/Akt通路，而该通路异常激活与多发性骨髓瘤（MM）发生、发展与耐药密切相关。我们最近发现，阿司匹林（ASA）经上调Bax、下调Bcl-2与VEGF诱导MM细胞凋亡，而三者恰是PI3K/Akt通路的下游分子。据此推测：PI3K/Akt通路可能是ASA抗MM作用的关键靶点。本项目拟继续：①利用siRNA干扰MM细胞PIK3CA基因，观察MM细胞系对ASA的敏感性和PIK3CA基因在ASA抗MM中的意义；②经体外与临床试验观察ASA的抗MM作用，探索PIK3CA在ASA个体化治疗MM中的价值；③观察ASA对骨髓基质细胞（BMSCs）粘附及其介导的硼替佐米（BTZ）耐药的影响；④分析ASA与BTZ在MM细胞中的相互作用，经检测Akt与Survivin蛋白，探索ASA对BTZ抗MM的增敏机制。本研究为ASA个体化治疗MM及作为BTZ的增敏剂提供依据。

The PI3K/Akt signaling pathway, activated by PIK3CA-encoded P110, occupied a pivotal role in the carcinogenesis and chemoresistance of multiple myeloma (MM). Recently we found that Aspirin (ASA) induced apoptosis of myeloma cells via upregulating Bax and inhibiting Bcl-2 and VEGF, which are the very downstream molecules of PI3K/Akt cascade, indicating that PI3K/Akt pathway may be the key target of ASA in MM. The study aims to further explore: ①the effect of ASA on myeloma cell lines without PIK3CA gene by siRNA and the expression of PIK3CA gene in anti-MM of ASA; ②the anticancer activity of ASA on primary myeloma cells in vitro & in vivo and the role of ASA's individualized therapy in MM; ③the influence of ASA on adhesion of myeloma cells and bortezomib (BTZ) resistance by stroma; ④the interaction of ASA and BTZ on MM cells and the chemosensitive mechanisms of ASA to BTZ via examination of Akt and Survivin. The results will provide the rationale for personalized treatment and chemosensitivity of ASA in MM.