TPH1 inhibits bladder tumorigenesis by targeting HIF-1α pathway in bladder cancer.

BACKGROUND

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.

OBJECTIVES

Our aim is to demonstrate the molecular mechanism of TPH1 in BCa carcinogenesis and development.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.