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PTTG1 通过增加 CXADR 表达增强溶瘤腺病毒 5 进入胰腺腺癌细胞。

PTTG1 Enhances Oncolytic Adenovirus 5 Entry into Pancreatic Adenocarcinoma Cells by Increasing CXADR Expression.

机构信息

Department of Clinical Laboratory, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China.

出版信息

Viruses. 2023 May 11;15(5):1153. doi: 10.3390/v15051153.

DOI:10.3390/v15051153
PMID:37243239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10223099/
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-PTTG1 and MIA PaCa-2-PTTG1 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-PTTG1 and MIA PaCa-2-PTTG1 cells and poor in BxPC-3-PTTG1 and MIA PaCa-2-PTTG1 cells. We used the OAd5 expressing GFP for transduction. As a result, the fluorescence intensity was enhanced in BxPC-3-PTTG1 and MIA PaCa-2-PTTG1 cells and decreased in BxPC-3-PTTG1 and MIA PaCa-2-PTTG1 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）在多种类型的肿瘤中过度表达，发挥癌基因的作用；它也可能成为肿瘤治疗的潜在靶点。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 在癌症治疗中的广阔前景，我们在这项研究中探讨了 PTTG1 对 PAAD 治疗的影响。癌症基因组图谱计划（TCGA）的数据显示，PTTG1 的高表达与胰腺癌的较高临床分期和较差的预后相关。此外，CCK-8 检测表明，在 BxPC-3-PTTG1 和 MIA PaCa-2-PTTG1 细胞中，吉西他滨和 5-氟尿嘧啶（5-FU）的 IC50 增加。TIDE 算法表明，在 PTTG1 高组中，免疫检查点阻断（ICBs）的效率较差。此外，我们发现 OAd5 在 BxPC-3-PTTG1 和 MIA PaCa-2-PTTG1 细胞中的效率增强，而在 BxPC-3-PTTG1 和 MIA PaCa-2-PTTG1 细胞中效率降低。我们使用表达 GFP 的 OAd5 进行转导。结果，OAd5 转导 24 小时后，BxPC-3-PTTG1 和 MIA PaCa-2-PTTG1 细胞中的荧光强度增强，而 BxPC-3-PTTG1 和 MIA PaCa-2-PTTG1 细胞中的荧光强度降低。荧光强度表明 PTTG1 增加了 OAd5 的进入。流式细胞术检测表明，PTTG1 增强了 OAd5 受体 CXADR 的表达。在 CXADR 敲低的情况下，PTTG1 未能进一步增强 OAd5 的转导。总之，PTTG1 通过增加细胞表面上的 CXADR 表达来增强 OAd5 对胰腺癌细胞的转导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/ddad18e3914d/viruses-15-01153-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/c03cf59e1c45/viruses-15-01153-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/e92d9ec9f539/viruses-15-01153-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/84dd1bfb0705/viruses-15-01153-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/6bd9d572473d/viruses-15-01153-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/4a518834ef48/viruses-15-01153-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/def3fdecb680/viruses-15-01153-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/ddad18e3914d/viruses-15-01153-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/c03cf59e1c45/viruses-15-01153-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/e92d9ec9f539/viruses-15-01153-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/84dd1bfb0705/viruses-15-01153-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/6bd9d572473d/viruses-15-01153-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/4a518834ef48/viruses-15-01153-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/def3fdecb680/viruses-15-01153-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0566/10223099/ddad18e3914d/viruses-15-01153-g007.jpg

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