Novel inhibitor of OCT1 enhances the sensitivity of human esophageal squamous cell carcinoma cells to antitumor agents.

Esophageal squamous cell carcinoma (ESCC) is one of the most fatal malignancies of the digestive system, and shows an especially high incidence in some regions of China. Octamer transcription factors are a family of transcription factors whose DNA-binding domain is a POU domain. OCT transcription factors (OCT-TFs) mediate maintenance of the pluripotency of embryonic stem cells. We measured expression of OCT-TFs in ESCC clinical specimens. Among the OCTs tested, OCT1 showed the highest expression in ESCC tissues. Using molecular docking, we discovered a small-molecule inhibitor, which we named "novel inhibitor of OCT1" (NIO-1), for OCT1. Treatment with NIO-1 inhibited recruitment of OCT1 to the promoter region of its downstream genes and, consequently, repressed OCT1 activation. Treatment with NIO-1 enhanced the susceptibility of ESCC cells to chemotherapeutic agents. Therefore, OCT1 may be a valuable target for ESCC treatment, and NIO-1 could be a promising therapeutic agent.