人参皂甙Rg3对胰腺癌SW-1990细胞皮下移植瘤血管生成拟态影响的研究

Effect of ginsenoside Rg3 on growth and vasculogenic mimicry of implanted human pancreatic cancer in nude mice

目的研究人参皂甙Rg3对胰腺癌SW-1990细胞皮下移植瘤生长及血管生成拟态的影响。方法用胰腺癌SW-1900细胞株建立裸鼠胰腺癌皮下移植瘤模型,分成4组:0.9%氯化钠溶液对照组、5 mg/kg人参皂甙Rg3组、10 mg/kg人参皂甙Rg3组、20mg/kg人参皂甙Rg3组,每组7只。各组裸鼠予腹腔注射给药,隔天1次,给药4周。给药结束后3d处死裸鼠,检测各组移植瘤的体积和重量;CD31/PAS染色观察移植瘤血管生成拟态的变化;荧光定量PCR和Western blot检测各组移植瘤钙粘蛋白(VE-Cadherin)、络氨酸激酶受体2(Eph A2)、基质金属蛋白2(MMP-2)、基质金属蛋白9(MMP-9)m RNA和蛋白表达水平。结果与对照组比较,20mg/kg人参皂甙Rg3组裸鼠胰腺癌皮下移植瘤体积减小、重量减轻(均P<0.05)。与对照组比较,5mg/kg人参皂甙Rg3组、10mg/kg人参皂甙Rg3组、20mg/kg人参皂甙Rg3组裸鼠胰腺癌皮下移植瘤拟态、正常血管生成均减少(均P<0.05),VE-Cadherin、Eph A2、MMP-2、MMP-9 m RNA和蛋白表达水平均降低(均P<0.05)。结论人参皂甙Rg3可抑制胰腺癌SW-1900细胞皮下移植瘤生长和血管生成拟态形成,可能是通过调控VE-Cadherin、Eph A2、MMP-2、MMP-9的表达发挥抗肿瘤作用。

Objective To investigate the effects of ginsenoside Rg3 on growth and vasculogenic mimicry of implanted human pancreatic cancer in nude mice. Methods Human pancreatic cancer SW- 1990 cells were inoculated subcutaneously in nude mice. The tumor bearing nude mice were divided into four groups with 7 mice in each group. The animals were injected intraperitoneally with saline control, 5 mg/kg, 10mg/kg and 20mg/kg ginsenosides Rg3 for 4 wk, respectively. The animals were sacrificed 3d after completion of the treatment. The weight and size of xenografts were measured, the vasculogenic mimicry was observed by immunohistochemistry with CD31/PAS staining, and the m RNA/protein expressions of VE- Cadherin, Eph A2,MMP- 2, MMP- 9 were detected by fluorescent RT- PCR and Western blot, respectively. Results Ginsenosides Rg3 significantly inhibited weight and size of transplanted tumors; and inhibited vasculogeic mimicry. The expression of VE- Cadherin, Eph A2, MMP- 2 and MMP- 9 m RNA and protein were down- regulated. Conclusion Rg3 can inhibit vasculogenic mimicry of transplanted human pancreatic cancer in nude mice, which may be associated with the down- regulation of VE- Cadherin, Eph A2, MMP9 and MMP2 expression.