反义VEGF基因及内皮抑素基因转染对人巨细胞肺癌生物学行为的影响

Abstract

目的 探讨反义VEGF基因和内皮抑素基因联合转染在抑制肿瘤血管生成和肿瘤生长转移中的作用。方法 反义VEGF121cDNA脂质体法转染人肺巨细胞癌细胞（PG-AS-VEGF），先行转基因细胞裸鼠异种移植，之后电脉冲介导PsectagA-内皮抑素基因转染，观察反义VEGF基因和内皮抑素转染对肿瘤血管生成和肿瘤生长转移的调节作用。结果 肿瘤内微血管密度在PG-AS-VEGF、转染空载体组分别为40.67±9.35和58.34±10.52(P＜0.05)；裸鼠体内接种PG-AS-VEGF细胞后18天，PG-AS-VEGF、转染空载体组肿瘤体积分别为(0.9779±0.2421)和(1.5210±0.4150)cm3(P＜0.05)；PG-AS-VEGF、转染空载体组淋巴结转移率分别为16.7％(2／12)和50％(6／12)(P＜0.05)。在肿瘤局部行PsectagA-内皮抑素基因转染的PG-AS-VEGF瘤，当肿瘤生长到21天时，肿瘤生长受到明显抑制，PsectagA-内皮抑素基因转染组与PsectagA空载体转染组肿瘤体积分别为(1.5889±1.1396)和(3.398±2.642)cm3(P＜0.05)；两者肿瘤淋巴结转移率分别为12.5％(1／8)和75％(6／8)(P＜0.05)。结论 内皮抑素基因转染对反义VEGF基因转染的PG细胞裸鼠体内生长和淋巴结自发性转移有协同抑制作用。

bjective To explore the co-operative inhibitory effect ofantisense VEGF gene and endostatin gene transfection on tumor angiogenesis, tumor growth and metastasis of lung cancer. Methods Antisense VEGF121 cDNA was transfected into PG cells(PG-AS-VEGF) by lipofectin. After PG-AS-VEGF cells were xenografted to nude mice, PsectagA-endostatin gene was transfected into nude mice by electric pulse mediation. The MVDs in tumors and tumor biological characteristics were observed. Results ①The MVD in PG-AS-VEGF tumor in nude mice was significantly lower than that in PG-vector tumor (PG-AS-VEGF and PG-vector: 40.67±9.35 and 58.34±10.52, respectively) in nude mice. ②There was no significant difference between the PG-vector tumor and PG-AS-VEGF tumor in early stage of the tumor growth in vivo. However, PG-AS-VEGF tumor grew significantly more slowly than PG-vector tumor after 18 days (P＜0.05). ③PG-AS-VEGF tumor could lead to regional and／or distant lymph node metastases (16.7％, 2／12）, which was much more infrequent than that in PG-vector group (50％, 6／12). ④ PG-AS-VEGF tumor growth was remarkably inhibited by endostatin gene transfected at site of the tumor inoculation as compared with the control group in nude mice (P＜0.05). ⑤The PG-AS-VEGF tumors transfected with the endostatin gene at site of the tumor inoculation(AST) could also produce much lower regional and／or distant lymph node metastases rate (12.5％, 1／8） than that in the PG-AS-VEGF tumor transfected with the PsectagA vector (ASP)(75％, 6／8). Conclusion Endostatin gene transfection could cooperatively inhibit the growth and spontaneous lymph node metastasis of antisense VEGF gene transfected PG cells in nude mice.