重组人血管内皮抑制素复合磷酸钙抗肿瘤骨水泥治疗肺癌骨转移的实验研究

Lung cancer is one of the most common malignant tumors, about 30-40% patients with lung cancer can occur bone metastasis that charactered by osteolytic destruction. Intractable pain, pathological fracture and nerve compression produced by bone metastasis are the choke points of basic research and clinical treatment currently. Percutaneous vertebroplasty ( PVP ) is widely used in bone metastatic tumor performed by interventional physicians. Traditional prototyping material of PVP is polymethyl methacrylate(PMMA),which has poor biocompatibility,low anti-tumor effect and high toxicity.We intend to combine calcium phosphate cement(CPC) and Endostar into advanced composite material in order to improve the prototyping material of PVP. The advanced composite material can both repair bone defect and has sustained-release effect for long-term inactivating tumor. Therefore, based on our pilot research and lung cancer cell line A549, this study is to investigate feasibility and reliability of the anvanced composite prototyping material for treating bone metastasis of lung cancer，which is expected to form new academic growing points and promote the basic research and clinical treatment of bone metastasis.

肺癌是世界范围内最常见的恶性肿瘤之一，约30-40%的肺癌患者会发生以溶骨性破坏为主的骨转移，肺癌骨转移产生的顽固性疼痛、病理性骨折及神经压迫症状是目前基础研究与临床诊疗的瓶颈。经皮椎体成形术(PVP)是近年来广泛应用于肿瘤骨转移治疗的介入手术，传统的PVP成形材料为聚甲基丙烯酸甲酯（PMMA），存在生物相容性差、抗肿瘤作用局限、生物毒性大等缺陷。本课题拟对PVP成形材料作相应改进，将生物相容性强、可降解的磷酸钙骨水泥（CPC）复合抗肺癌药物重组人血管内皮抑制素（Endostar）形成新型复合材料，渴望达到既能修复骨缺损又能缓释药物以长期灭活肿瘤的理想效果。本研究以前期研究为基础，以CPC负载Endostar复合材料、肺癌细胞株A549为研究对象，探索CPC负载Endostar复合材料治疗肺癌骨转移的可行性、可靠性，以期推动肺癌等恶性肿瘤骨转移的基础研究和临床诊疗。

肺癌是世界范围内最常见的恶性肿瘤之一，约30-40%的肺癌患者会发生以溶骨性破坏为主的骨转移，肺癌骨转移产生的顽固性疼痛、病理性骨折及神经压迫症状是目前基础研究与临床诊疗的瓶颈。本研究通过体外和体内实验观察可降解的磷酸钙骨水泥（CPC）复合抗肺癌药物重组人血管内皮抑制素（Endostar）形成新型复合材料抗肿瘤修复骨缺损的效果。体外研究结果发现：抗肿瘤骨水泥CPC+Endostar和CPC+PLGA+Endostar的机械性能（粒径、抗弯、抗压、孔隙率等）与CPC相比不存在差异。抗肿瘤骨水泥CPC+Endostar和CPC+PLGA+Endostar具有抑制细胞增殖、促进凋亡和细胞周期阻断于G1期；并且破骨相关基因CXCL2、TGF-β1、IGF-1、IL-6和RANKL 表达量明显降低；成骨能力ALP活性明显增强。体外研究结果表明：随着动物治疗时间的延长，3周的CPC+ PLGA+ENDO肿瘤组织的基因和蛋白TRAP、RANKL、CASPASE3表达量低于其他组别，OPN、BCL2基因和蛋白表达量高于其他组别。3周的CPC+ PLGA+ENDO肿瘤组织HE和TUNEL染色结果得出：组织坏死和细胞凋亡高于其他组。CPC负载Endostar复合材料治疗肺癌骨转移是可行的，可推动肺癌等恶性肿瘤骨转移的基础研究和临床诊疗。