Pancreatic carcinoma is one of the most aggressive tumors, and, being refractory to conventional therapies, is an excellent target for new therapeutic approaches. Based on our previous finding of high HMGA1 expression in pancreatic cancer cells compared to normal pancreatic tissue, we evaluated whether suppression of HMGA1 protein expression could be a treatment option for patients affected by pancreatic cancer. Here we report that HMGA1 proteins are overexpressed in pancreatic carcinoma cell lines, and their downregulation through an adenovirus carrying the HMGA1 gene in an antisense orientation (Ad Yas-GFP) results in the death of three human pancreatic carcinoma cell lines (PANC1, Hs766T and PSN1). Pretreatment of PANC1 and PSN1 cells with Ad Yas-GFP suppressed and reduced, respectively, their ability to form xenograft tumors in nude mice. To further verify the role of HMGA1 in pancreatic tumorigenesis, we used a HMGA1 antisense phosphorothioate oligodeoxynucleotide (ODN); its addition induced a decrease in HMGA1 protein levels and a significant reduction of the proliferation rate of PANC1-, Hs766T- and PSN1-treated cells. Therefore, suppression of HMGA1 protein synthesis by an HMGA1 antisense approach seems to be a feasible treatment strategy in pancreatic carcinomas.

中文翻译：

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在临床前模型中基于抑制HMGA1蛋白合成的人类胰腺癌治疗。

胰腺癌是最具侵略性的肿瘤之一，并且对传统疗法无能为力，是新治疗方法的理想靶标。基于我们先前在胰腺癌细胞中与正常胰腺组织相比高HMGA1表达的发现，我们评估了抑制HMGA1蛋白表达是否可以作为受胰腺癌影响的患者的治疗选择。在这里，我们报道HMGA1蛋白在胰腺癌细胞系中过表达，并且它们通过在反义方向上携带HMGA1基因的腺病毒（Ad Yas-GFP）的下调导致三种人类胰腺癌细胞系（PANC1，Hs766T和PSN1）。用Ad Yas-GFP预处理PANC1和PSN1细胞分别抑制和降低了它们在裸鼠中形成异种移植肿瘤的能力。为了进一步验证HMGA1在胰腺肿瘤发生中的作用，我们使用了HMGA1反义硫代磷酸酯寡脱氧核苷酸（ODN）；它的加入导致HMGA1蛋白水平降低，PANC1，Hs766T和PSN1处理的细胞的增殖速率显着降低。因此，通过HMGA1反义方法抑制HMGA1蛋白合成似乎是胰腺癌的可行治疗策略。