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Ⅳ型胶原酶(包括MMP-2和MMP-9)与肿瘤的侵袭转移和恶性进展密切相关. 通过构建可在真核细胞内质网表达抗Ⅳ型胶原酶 scFV M97抗体基因的真核表达载体, 应用脂质体LipofectAMINE法对人高转移性肺巨细胞癌PG细胞系进行基因治疗.研究 结果表明,细胞内表达 scFv M97对 PG细胞 Ⅳ型胶原酶分泌、 PG细胞生长及体外侵袭 能力具有显著的抑制作用,并能明显降低PG细胞裸鼠体内成瘤性,延长动物存活时间. 以上结果提示胞内抗体技术可以在蛋白加工、分泌这一关键步骤从根本上抑制Ⅳ型胶 原酶的活性,在肿瘤基因治疗中具有重要的应用前景。
Type IV collagenase (including MMP-2 and MMP-9) is closely related to tumor invasion and metastasis and malignant progression. By constructing a eukaryotic expression vector expressing the anti-type Ⅳ collagenase scFV M97 antibody in the endoplasmic reticulum of Eukaryotic cells, liposome-mediated LipofectAMINE method was used to genetically treat human highly metastatic lung giant cell carcinoma PG cell line. The results showed that intracellular expression of scFv M97 on PG cells collagenase type Ⅳ, PG cell growth and in vitro invasive ability significantly inhibited, and can significantly reduce PG cell nude mice in vivo tumorigenicity and prolong animal survival time. The above results suggest that the intracellular antibody technology can fundamentally inhibit the activity of type IV collagenase in the key step of protein processing and secretion and has important application prospect in tumor gene therapy.