沉默血管生成素-2表达对人肺腺癌细胞生物学特性的影响

BACKGROUND AND OBJECTIVE: It is well-known that angiopoietin-2 (Ang-2) plays an important role in the formation of the blood vascular system. Angiopoietin is involved in many diseases about angiogenesis such as tumor, so may have great prospects for the treatment of these diseases. The aim of this study is to evaluate the influence of inhibiting Ang-2 via adeno-associated virus induced RNA interference (RNAi) on the biological characteristics of bronchogenic adenocarcinoma. METHODS: AAV-Ang-2(shRNA) driven by H1 promoter was constructed to transfect A549 cell line. Normal and AAV-Null cell line were utilized in the control groups. The influence of RNAi on Ang-2 expression as well as the growth rate, tumorigenic efciency, proliferation rate, apoptosis, and microvessel density of A549 cell line were analyzed. RESULTS: In vitro experiment indicated that the Ang-2 expression level (P < 0.001) and growth rate (P < 0.001) of A549 cell line 48 h transfected with AAV-Ang-2(shRNA) were signifcantly lower than those in the normal and AAV-Null cell lines. Cell cycle analysis showed the proliferation index (PI) of normal, AAV-Null, and AAV-Ang-2(shRNA) transfected A549 cell line were 0.51±0.43, 0.48±0.29, and 0.26±0.31, respectively, which indicated the PI of AAV-Ang-2(shRNA) transfected cell line was signifcantly lower, compared with the normal and AAV-Null cell lines. In vivo experiment exhibited that AAV-Ang-2(shRNA) transfected cell line possessed a lower mass and volumn of tumor relative to two control groups. In addition, the apoptosis index (AI) of AAV-Ang-2(shRNA) transfected, normal, and AAV-Null cell lines were (5.98±3.11)%, (7.51±4.42)% and (17.06±7.43)% respectively, which manifested that AAV-Ang-2(shRNA) transfected cell line possessed a higher AI (P=0.005, P=0.007). A lower percentage of PCNA-positive cell was observed in AAV-Ang-2(shRNA) transfected cell line (92.75±9.7)% as well, compared with the normal (85.8±11.8)% and AAV-Null (69.8±16.5)% cell lines. CONCLUSION: AAV-mediated expression of shRNA signifcantly reduces concentration of Ang-2 in A549 cell line, lowers proliferation and growth rate and induce.apoptosis of A549 cell line.