Antisense oligonucleotides to gastrin inhibit growth of human pancreatic cancer.
Antisense oligonucleotides to gastrin inhibit growth of human pancreatic cancer.
复制标题
胃泌素反义寡核苷酸抑制人胰腺癌的生长。
DOI：
10.1016/s0304-3835(98)00279-1
复制
发表时间：
1999
期刊：
影响因子：
9.7
通讯作者：
Zagon,IS
中科院分区：
文献类型：
--
作者：
Smith,JP;Verderame,MF;Zagon,IS
人胰腺癌是由胃泌素的自分泌产生刺激的。在这项研究中，胃泌素的反义寡核苷酸的管理对胰腺癌的生长在体外和体内的影响进行了评估。将培养物中的对数期BxPC-3人胰腺癌细胞暴露于浓度递增（0.5-10 μM）的合成20聚体反义硫代磷酸寡核苷酸（胃泌素）48 h，并通过细胞增殖试验评估生长。与用稀释剂或具有与抗胃泌素寡核苷酸相同组成的随机序列处理的细胞相比，抗胃泌素寡核苷酸以剂量相关的方式抑制生长高达88%。携带BxPC-3异种移植物的体内裸鼠每天瘤内注射0.1 ml抗胃泌素（5 μM）、乱序序列对照硫代磷酸寡核苷酸（5 μM）或缓冲液，持续14天。与对照组相比，抗胃泌素治疗组小鼠的肿瘤体积和重量明显较小，放射免疫测定法检测到的胃泌素也较少。这些结果支持胃泌素作为人胰腺癌生长的刺激肽的作用。胃泌素反义寡核苷酸可能在胰腺癌患者的未来治疗中发挥作用。
Human pancreatic cancer is stimulated by the autocrine production of gastrin. In this study, the effects of administration of antisense oligonucleotides to gastrin on growth of pancreatic cancer were evaluated in vitro and in vivo. Log phase BxPC-3 human pancreatic cancer cells in culture were exposed to increasing concentrations (0.5–10 μM) of a synthetic 20-mer antisense phosphorothioate oligonucleotide to gastrin for 48 h and growth was assessed by the cellular proliferation assay. Growth was inhibited up to 88% by anti-gastrin oligonucleotides in a dose-related fashion compared to cells treated with diluent or a randomized sequence with the same composition as the anti-gastrin oligonucleotide. In vivo nude mice bearing BxPC-3 xenografts were treated daily for 14 days with a 0.1-ml intratumoral injection of either anti-gastrin (5 μM), the scrambled sequence control phosphorothioate oligonucleotide (5 μM), or buffer. Tumors from the anti-gastrin-treated mice were significantly smaller in volume and weight and had less gastrin detected by radioimmunoassay than either controls. These results support the role of gastrin as a stimulatory peptide for growth of human pancreatic cancer. Antisense oligonucleotide to gastrin may have a role in the future treatment of patients with pancreatic cancer.