@article{mbs:/content/journal/jgv/10.1099/jgv.0.001752, author = "Nishimae, Fumitaka and Sakurai, Fuminori and Ono, Ryosuke and Onishi, Rika and Takayama, Kosuke and Mizuguchi, Hiroyuki", title = "A dopamine antagonist, domperidone enhances the replication of an oncolytic adenovirus in human tumour cells", journal= "Journal of General Virology", year = "2022", volume = "103", number = "6", pages = "", doi = "https://doi.org/10.1099/jgv.0.001752", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001752", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", keywords = "pancreatic tumor cells", keywords = "oncolytic adenovirus", keywords = "domperidone", keywords = "chemical library", eid = "001752", abstract = "Oncolytic adenoviruses (OAds) have attracted much attention as novel anticancer agents. Numerous studies have examined the antitumour effects of combinational use of an OAd and anticancer agents; however, few chemical compounds enhancing OAd infection have been reported. In this study, we screened a food and drug administration (FDA)-approved drug library containing 1134 small chemical compounds to identify chemical compounds that enhance OAd replication in human tumour cells. We found that domperidone, a dopamine D2 receptor antagonist, significantly enhanced the replication of an OAd in human tumour cells, including human pancreatic tumour cells, by two–fivefold, resulting in improvement of OAd-mediated tumour cell killing activities. The E1A mRNA levels were significantly increased in domperidone-pre-treated cells following OAd infection, which contributed to the promotion of OAd replication. However, mRNA levels of the dopamine D2 receptor (DRD2), which is known to be a target molecule of domperidone, were undetectable in most of the tumour cells by real-time reverse transcription (RT)-PCR analysis, indicating that domperidone promoted OAd replication by acting on a molecule other than DRD2. This study provides important clues for the improvement of OAd-mediated cancer therapy.", }