Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Laboratório de Farmacologia Aplicada, Escola de Ciências da Saúde e da Vida, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Mol Cell Biochem. 2022 Aug;477(8):2047-2057. doi: 10.1007/s11010-022-04425-0. Epub 2022 Apr 16.
As alterations in purinergic signaling have been observed in bladder diseases, we aimed to assess the potential prognostic role of purinergic receptors in bladder cancer in a translational approach based on clinical databases and in vitro data. The prognostic role of purinergic receptors in the survival of patients with bladder cancer and the expression profile of the altered P2 receptors in normal and in tumor samples were determined using The Cancer Genome Atlas databank. In T24 and RT4 human bladder cancer cell lines, the P2 purinergic receptors were characterized by RT-PCR and RT-qPCR analysis including radiotherapy exposure as treatment. The cell number and the cumulative population doubling were also assessed. The expression profile of P2X6 receptor in the cancer pathological stage and in the nodal metastasis status was in agreement with Kaplan-Meier analysis, indicating that high expression of this receptor was related to an increased survival rate in patients with bladder cancer. Of all the P2 receptors expressed on T24 cell line, P2X6 presented high expression after radiotherapy, while it was not altered in RT4 cells. In addition, irradiation promoted a decrease of T24 cell number, but did not change the cell number of RT4 after the same time and radiation dose. Along 7 days after irradiation exposure, both cells regrew. However, while P2X6 receptor was downregulated in T24 cells, it was upregulated in RT4 cells. Our findings indicated that high P2X6 receptor expression induced by radiation in T24 cell line may predict a good survival prognostic factor.
由于嘌呤能信号的改变已在膀胱疾病中观察到，我们旨在基于临床数据库和体外数据的转化方法来评估嘌呤能受体在膀胱癌中的潜在预后作用。使用癌症基因组图谱数据库确定了嘌呤能受体在膀胱癌患者生存中的预后作用，以及改变的 P2 受体在正常和肿瘤样本中的表达谱。在 T24 和 RT4 人膀胱癌细胞系中，通过 RT-PCR 和 RT-qPCR 分析（包括放射治疗暴露作为治疗）来表征 P2 嘌呤能受体。还评估了细胞数量和累积群体倍增。P2X6 受体在癌症病理分期和淋巴结转移状态中的表达谱与 Kaplan-Meier 分析一致，表明该受体的高表达与膀胱癌患者生存率的提高有关。在 T24 细胞系上表达的所有 P2 受体中，P2X6 在放射治疗后表达较高，而在 RT4 细胞中未改变。此外，照射促进 T24 细胞数量减少，但在相同时间和辐射剂量后不会改变 RT4 细胞的数量。照射暴露后 7 天，两种细胞都重新生长。然而，虽然 P2X6 受体在 T24 细胞中下调，但在 RT4 细胞中上调。我们的研究结果表明，T24 细胞系中辐射诱导的高 P2X6 受体表达可能预示着良好的生存预后因素。
