整合素在肿瘤细胞增殖和肿瘤组织血管生成中起着极为重要的作用，是抗肿瘤药物开发的一个重要靶点。我们前期研究显示，肿瘤的放疗抵抗与整合素的表达密切相关，细胞实验表明，用sirna敲低（know down）整合素，能降低肿瘤细胞的放疗抵抗。在本项目中，我们构建了抗整合素抗体的pei-dna-avidin-biotin-antibody的基因导向系统，以转座子spleeping beauty为载体的shrna的表达系统特异性导向肿瘤细胞，敲低神经胶质瘤细胞u87mg、乳腺癌细胞mda-mb-435和mcf7的整合素，特异性降低肿瘤的放射抵抗和肿瘤的增殖，加上立体定位放疗手段，在细胞和乳腺癌动物模型上，达到高效和特异地杀伤肿瘤，为进一步深入研究肿瘤放射抵抗的分子机理奠定了基础。

integrin ανβ3 plays a critical role in tumor angiogenesis and proliferation. it is a very important and promising molecular targe for development of novel antineoplastic agents. our preliminary data revealed that the expression of integrin ανβ3 is positively correlated with a variety of tumor radiation-resistance. in vitro cell studies further showed that the sensitivity of tumor cells to radiation therapy could be significantly improved by knocking down cell integrin ανβ3 level. so, we developed a novel shrna delivery system to knock down integrin ανβ3, thus to radiosensitize tumors and achieve better radiation treatment efficacy. in detail, the gene delivery system, pei-dna-avidin-biotin-anti-integrin ανβ3 antibody which contains integrin ανβ3-specific shrna and transposon (sleeping beauty) was constructed first. then it was used to specifically modulate human glioma u87mg, breast cancer mda-mb-435 and mcf-7 integrin ανβ3 expression in vitro and in vivo. through knocking down integrin ανβ3, the tumors were destroyed more efficiently by radiation in vitro and in vivo. this research provide us new knowledge to understand the molecular basis and mechanism of tumor radiation-resistance.

整合素在肿瘤细胞增殖和肿瘤组织血管生成中起着极为重要的作用，是抗肿瘤药物开发的一个重要靶点。我们前期研究显示，肿瘤的放疗抵抗与整合素的表达密切相关，细胞实验表明，用sirna敲低（know down）整合素，能降低肿瘤细胞的放疗抵抗。在本项目中，我们构建了抗整合素抗体的pei-dna-avidin-biotin-antibody的基因导向系统，以转座子spleeping beauty为载体的shrna的表达系统特异性导向肿瘤细胞，敲低神经胶质瘤细胞u87mg、乳腺癌细胞mda-mb-435和mcf7的整合素，特异性降低肿瘤的放射抵抗和肿瘤的增殖，加上立体定位放疗手段，在细胞和乳腺癌动物模型上，达到高效和特异地杀伤肿瘤，为进一步深入研究肿瘤放射抵抗的分子机理奠定了基础。