Ren Jianwei, Mo Zhiting, Deng Xia, Ren Minghui, Ren Hailong, Jin Jie, Zhang Huihui
Department of Basic Medicine, Tibet University Medical College, Lhasa, Tibet 850000, China.
Department of Clinical Laboratory, Lhasa People's Hospital, Lhasa, Tibet 850000, China.
Asian Biomed (Res Rev News). 2024 Sep 20;18(4):171-179. doi: 10.2478/abm-2024-0023. eCollection 2024 Aug.
BCa is the most common cancer of the urinary system. TPH1 has been reported to be associated with distinct tumorigenesis. However, the role of TPH1 in BCa remains to be clarified.
Our aim is to demonstrate the molecular mechanism of TPH1 in BCa carcinogenesis and development.
In research, we explored the effect of TPH1 on T24 cells. Colony formation, soft agar, and cell proliferation assays were used to determine the survival and proliferative capacity of cells. Moreover, TPH1 cell lines were analyzed using , and the recovery experiment was conducted. Realtime fluorescence quantitative PCR (qPCR) and Western blot were used to detect HIF-1α mRNA levels and TPH1 protein.
The TPH1 expression is lower in tumor tissues than in normal tissues. Colony formation, soft agar, and cell proliferation assays revealed that the overexpression of TPH1 declined cells survival. Moreover, the deficiency of TPH1 increased the number of clones. These results suggested that survival rate of TPH1 overexpression was repressed in cells. In addition, we found that HIF-1α activity was significantly downregulated with an increase in TPH1. The transcriptional activity of survivin was increased with TPH1 cells. Then, the proliferative ability of TPH1 cells was almost similar to the wild type levels with the treatment of LW6, TPH1 might play a major role to repress HIF-1α activity.
Taken together, these results suggested that increasing TPH1 activity could inhibit survival and proliferation of cells via HIF-1α pathway. TPH1 may be a potential target for human BCa therapy.
膀胱癌是泌尿系统最常见的癌症。据报道，色氨酸羟化酶1（TPH1）与不同的肿瘤发生有关。然而，TPH1在膀胱癌中的作用仍有待阐明。
我们的目的是阐明TPH1在膀胱癌发生发展中的分子机制。
在研究中，我们探讨了TPH1对T24细胞的影响。采用集落形成、软琼脂和细胞增殖试验来确定细胞的存活和增殖能力。此外，使用 分析TPH1细胞系，并进行恢复实验。采用实时荧光定量PCR（qPCR）和蛋白质免疫印迹法检测缺氧诱导因子-1α（HIF-1α）mRNA水平和TPH1蛋白。
肿瘤组织中TPH1的表达低于正常组织。集落形成、软琼脂和细胞增殖试验表明，TPH1的过表达降低了细胞存活率。此外，TPH1的缺失增加了克隆数。这些结果表明，TPH1过表达的细胞存活率受到抑制。此外，我们发现随着TPH1的增加，HIF-1α活性显著下调。生存素的转录活性在TPH1细胞中增加。然后，用LW6处理后，TPH1细胞的增殖能力几乎与野生型水平相似，TPH1可能在抑制HIF-1α活性中起主要作用。
综上所述，这些结果表明，增加TPH1活性可通过HIF-1α途径抑制细胞的存活和增殖。TPH1可能是人类膀胱癌治疗的潜在靶点。
