重组人内皮抑素腺病毒对裸鼠胰腺癌移植瘤的抑制作用

Inhibitory effects of recombinant adenovirus carrying human endostatin gene on the growth of human pancreatic carcinoma xenograft in nude mice

目的探讨重组人内皮抑素腺病毒(Ad-endo)对人胰腺癌移植瘤生长的影响。方法人胰腺癌Capan-2细胞经Ad-endo感染后,PT-PCR方法检测人内皮抑素基因的表达。收集Ad-endo感染Capan-2细胞的条件培养液,观察其对人脐静脉血管内皮细胞(HUVEC)体外增殖的影响。建立人胰腺癌Capan-2细胞移植瘤模型,观察Ad-endo对胰腺癌移植瘤生长的抑制作用,分析肿瘤内微血管密度的变化情况。结果RT-PCR方法检测到人内皮抑素基因在Capan-2细胞的表达,Ad-endo感染Capan-2细胞的条件培养液能明显抑制HUVEC的增殖。Ad-endo显著减缓了人胰腺癌Capan-2细胞移植瘤生长(P<0.05),同时也明显减少了肿瘤组织微血管密度(P<0.05)。结论腺病毒介导的人内皮抑素基因能明显抑制胰腺癌裸鼠移植瘤的生长与血管生成。

Objective To evaluate the inhibitory effect of recombinant adenovirus carrying human endostatin gene （Ad-endo） on the growth of human pancreatic carcinoma xenograft in nude mice.Methods The expression of endostatin in human pancreatic carcinoma Capan-2 cells was examined by RT-PCR after infection with Ad-endo.The supernatants of Capan-2 cells were collected after 48 h of infection with Ad-endo as the conditioned medium for human umbilical vein endothelial cells （HUVECs）,whose proliferation in vitro was assayed.Capan-2 cell xenografts were established to determine the antitumoral effects of Ad-endo in vivo.The intratumoral microvessel density （MVD） was evaluated using CD31 staining.Results The expression of endostatin gene was detected by PT-PCR in infected Capan-2 cells.The conditioned medium from Ad-endo-infected cells significantly inhibited HUVEC proliferation （P0.05）.Ad-endo significantly suppressed the growth of Capan-2 tumor xenografts in nude mice （P0.05）,and the MVD decreased significantly in the treated tumor （P0.05） as compared with that in the control group.Conclusion Adenovirus carrying human endostatin gene produces inhibitory effects on the growth of human pancreatic carcinoma tumors in nude mice.