【摘要】 目的:观察血小板源生长因子(PDGF)B链基因(PDGF-B)的三链形成寡核苷酸(triplex forming oligonucleotide,TFO)PDGF-TFO和血管内皮生长因子(VEGF)反义寡核苷酸(antisense oligonucleotide,AON)VEGF-AON对大鼠脑胶质瘤生长的抑制作用。方法:36只雄性SD大鼠,分为4组,所有大鼠均在立体定向导引下行右尾状核区微量灌注含1×106C6胶质瘤细胞的生理盐水20μl。在细胞接种后第8天,实验Ⅰ组6只大鼠原位注射含PDGF-TFO 1.5 mg的20μl生理盐水,实验Ⅱ组12只和实验Ⅲ组12只大鼠则分别原位注射含PDGF-TFO 1.5 mg+VEGF-AON 0.125 mg和PDGF-TFO 1.5 mg+VEGF-AON 0.25 mg的20μl生理盐水。以后每隔72 h原位注射相同剂量的药物1次,共注射3次。对照组6只大鼠仅在相同时间原位注射20μl生理盐水。实验3周时处死所有大鼠,观察肿瘤的生长情况,定性和定量观察肿瘤PDGF-B、VEGF和肿瘤核增殖抗原(PCNA)表达。结果:实验Ⅰ组的成瘤抑制率为53.1%,实验Ⅱ组为81.4%,实验Ⅲ组为93.1%,3组比较有明显差异(P<0.01)。PDGF-TFO对C6胶质瘤细胞PDGF-B、VEGF、PCNA表达有明显的抑制作用;联合应用PDGF-TFO和VEGF-AON能更好地抑制PDGF-B、VEGF、PCNA表达。结论:联合应用PDGF-TFO和VEGF-AON比单用PFGF-TFO能更有效地抑制肿瘤生长。更多还原

【Abstract】 Objective:To observe the inhibitory effect of triplex forming oligonucleotede（TFO） of PDGF-B chain combined with antisense oligonucleotide（AON） of VEGF on glioma growth in rats.Methods: Thirty-six male SD rats received 1×10⁶ C₆ glioma cells/20 μl normal saline into the right caudate putamen by stereotactic technique.GroupⅠ（n=6） was treated in situ with 1.5 mg/20 μl TFO for 3 times on 8,11 and 14 d after glioma cell inoculation.Group Ⅱ（n=12） and Ⅲ（n=12） were respectively treated with TFO 1.5 mg+AON 0.125 mg/20 μl and TFO 1.5 mg+AON 0.250 mg/20 μl for 3 times on 8,11 and 14 d after glioma cell inoculation.Control group（n=6） was treated with 20 μl saline for 3 times at the same time pionts.Three weeks after cell inoculation,all rats were sacrificed to observe tumor growth and to determine the expression of PDGF-B,VEGF and PCNA.Results: The inhibition rate of tumor growth was 53.1% in groupⅠ,81.4% in group Ⅱ and 93.1% in group Ⅲ,with significant difference found between the 3 groups（P<0.01）.PDGF-TFO had obvious inhibitory effect on the expression of PDGF-B,VEGF and PCNA in C₆glioma cells;and PDGF-TFO combined with VEGF-AON had more potent inhibitory effect on the expression of PDGF-B,VEGF and PCNA in C₆glioma cells.Conclusion: PDGF-TFO combined with VEGF-AON has more potent inhibitory effect on tumor growth than PDGF-TFO alone.更多还原