腺病毒Ad-pig3RRP-PIAS3对辐射诱导肺腺癌细胞转移的抑制作用及其机制研究

Radiotherapy plays an important role in the tumor treatment. However, recent studies showed that radiation could promote the invasion of tumor cells although the killing effect of radiation was definite. Our recent study indicated that radiation could enhance the in vitro invasion and in vivo metastasis of lung adenocarcinoma cells (A549 cells), and this effect depended on raidiation-induced STAT3 activation. For this reason, it will be very significant to explore an approach to blocking radiation-induced STAT3 activation and subsequently inhibit radiation-induced tumor cells metastasis. We also found that radiation could induce the expression increasing of PIG3 gene in a dose dependent manner. This result implied that the promotor of PIG3 gene contained a radiosensible area, which could initiate the expression of its downstream gene when cells were irradiated. Based on these findings, this program intends to find the radiosensible area of PIG3 promotor, and subsequently link this area with the cDNA sequence of PIAS3 (protein inhibitor of activated STAT3), which was finally cloned into the adenovirus vector to construct a radiosensible adenovirus vector encoding PIAS3 (Ad-pig3RRP-PIAS3). This program will try to lay the foundation for lung adenocarcinom radiotherapy combinding Ad-pig3RRP-PIAS therapy.

放疗在肿瘤治疗中起重要作用，然而近年来发现辐射在杀伤肿瘤细胞的同时，还能促进多种肿瘤细胞侵袭。本课题组最新研究表明，辐射可促进肺腺癌A549体外侵袭和体内转移，且此侵袭能力增强依赖于辐射诱导的STAT3活性增加。因此，探索特异抑制辐射诱导STAT3活化的手段从而阻断其诱导的肿瘤细胞转移非常有意义。课题组同期研究发现辐射可诱导PIG3基因表达剂量依赖性升高，提示其启动子包含辐射敏感区域，可在受到辐射时特异启动下游基因表达。基于上述发现，本项目拟利用双荧光报告载体方法，确定PIG3基因启动子区的辐射敏感区域，将其与PIAS3蛋白（STAT3活性抑制蛋白）cDNA序列连接后克隆至腺病毒载体，构建辐射敏感PIAS3腺病毒表达载体Ad-pig3RRP-PIAS3，为进一步探索肺腺癌放疗联合Ad-pig3RRP-PIAS3治疗的新方法奠定基础。

本研究旨在探索特异抑制辐射诱导 STAT3 活化的手段从而阻断其诱导的肺腺细胞转移。研究确定了PIG3基因启动子区的辐射敏感区域，并将其与PIAS3蛋白cDNA序列连接后克隆至腺病毒载体，构建了辐射敏感的PIAS3腺病毒表达载体Ad-pig3RRP-PIAS3，并确定了其对辐射诱导肺腺癌细胞转移的抑制作用。发表文章9篇，其中3篇英文，会议论文4篇；其中8篇文章和4篇会议论文标注基金号。