Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, P.R. China.
Int J Mol Med. 2012 Dec;30(6):1403-9. doi: 10.3892/ijmm.2012.1133. Epub 2012 Sep 19.
Esophageal cancer is an intractable disease due to late diagnosis, high incidence of post-surgical locoregional recurrence and frequent distant metastasis. Oncolytic adenovirus (Ad) vectors are a promising method for cancer treatment. The H101 virus is a recombinant Ad which has replication-selective properties and replicates only in tumor cells. The coxsackievirus and adenovirus receptor (CAR) is considered a surrogate marker that monitors the outcome of Ad-mediated gene therapy. Accumulating evidence indicates that CAR expression levels are lower in various types of tumors such as ovarian, lung, breast and bladder when compared to their normal counterparts. In this study, we reported that trichostatin A (TSA) induced the expression of CAR in esophageal squamous cell carcinoma (ESCC) cell lines through the MAPK/ERK1/2 signaling pathway. The expression levels of CAR were positively related with the antitumor activity of H101. Our results suggest that TSA increases the antitumor activity of the oncolytic adenovirus H101 through the MAPK/ERK pathway.
食管癌由于诊断较晚，术后局部区域复发率高，远处转移频繁，因此是一种难治性疾病。溶瘤腺病毒（Ad）载体是一种很有前途的癌症治疗方法。H101 病毒是一种重组腺病毒，具有复制选择性，只能在肿瘤细胞中复制。柯萨奇病毒和腺病毒受体（CAR）被认为是监测腺病毒介导的基因治疗结果的替代标志物。越来越多的证据表明，与正常组织相比，CAR 在卵巢癌、肺癌、乳腺癌和膀胱癌等各种类型的肿瘤中的表达水平较低。在这项研究中，我们报告了曲古抑菌素 A（TSA）通过 MAPK/ERK1/2 信号通路诱导食管鳞癌细胞系中 CAR 的表达。CAR 的表达水平与 H101 的抗肿瘤活性呈正相关。我们的结果表明，TSA 通过 MAPK/ERK 通路增加了溶瘤腺病毒 H101 的抗肿瘤活性。
