PDF(Pubmed)
Abstract：
Pituitary tumor-transforming gene 1 (PTTG1) is overexpressed in various types of tumors and functions as an oncogene; it could also be a potential target in tumor therapy. Meanwhile, the high mortality of pancreatic adenocarcinoma (PAAD) largely depends on the limited effectiveness of therapy. Based on the promising potential of PTTG1 in cancer treatment, we explored the influence of PTTG1 on the treatment of PAAD in this study. The Cancer Genome Atlas Program (TCGA) data showed that higher expression of PTTG1 was associated with higher clinical stages and worse prognosis of pancreatic cancer. In addition, the CCK-8 assay showed that the IC50 of gemcitabine and 5-fluorouracil (5-FU) was increased in BxPC-3-PTTG1high and MIA PaCa-2-PTTG1high cells. The TIDE algorithm indicated that the immune checkpoint blockades\' (ICBs) efficiency is poor in the PTTG1 high group. Furthermore, we found that the efficiency of OAd5 was enhanced in BxPC-3-PTTG1high and MIA PaCa-2-PTTG1high cells and poor in BxPC-3-PTTG1low and MIA PaCa-2-PTTG1low cells. We used the OAd5 expressing GFP for transduction. As a result, the fluorescence intensity was enhanced in BxPC-3-PTTG1high and MIA PaCa-2-PTTG1high cells and decreased in BxPC-3-PTTG1low and MIA PaCa-2-PTTG1low cells 24 h after OAd5 transduction. The fluorescence intensity indicated that PTTG1 increased OAd5 entry. The flow cytometry assay showed that OAd5 receptor CXADR expression was enhanced by PTTG1. PTTG1 failed to further enhance OAd5 transduction in the case of CXADR knockdown. In summary, PTTG1 enhanced OAd5 transduction into pancreatic cancer cells by increasing CXADR expression on the cell surface.
摘要：
垂体肿瘤转化基因1（PTTG1）在各种类型的肿瘤中过表达，并作为癌基因发挥作用；它也可能是肿瘤治疗的潜在靶标。同时,胰腺腺癌(PAAD)的高死亡率在很大程度上取决于治疗效果有限.基于PTTG1在癌症治疗中的潜力，本研究探讨了PTTG1对PAAD治疗的影响。癌症基因组图谱计划（TCGA）数据显示，PTTG1的高表达与胰腺癌的临床分期和预后较差有关。此外,CCK-8分析显示,在BxPC-3-PTTG1high和MIAPaCa-2-PTTG1high细胞中,吉西他滨和5-氟尿嘧啶(5-FU)的IC50增加.TIDE算法表明，PTTG1高组的免疫检查点阻断（ICB）效率较差。此外，我们发现OAd5在BxPC-3-PTTG1high和MIAPaCa-2-PTTG1high细胞中的效率增强，而在BxPC-3-PTTG1low和MIAPaCa-2-PTTG1low细胞中的效率较差。我们使用表达GFP的OAd5进行转导。因此,OAd5转导后24小时，BxPC-3-PTTG1high和MIAPaCa-2-PTTG1high细胞的荧光强度增强，而BxPC-3-PTTG1low和MIAPaCa-2-PTTG1low细胞的荧光强度降低。荧光强度表明PTTG1增加了OAd5进入。流式细胞术检测显示OAd5受体CXADR表达被PTTG1增强。在CXADR敲低的情况下,PTTG1未能进一步增强OAd5转导。总之,PTTG1通过增加细胞表面的CXADR表达来增强OAd5向胰腺癌细胞的转导。
