A dopamine antagonist, domperidone enhances the replication of an oncolytic adenovirus in human tumour cells.
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| 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.
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| Authors | Fumitaka Nishimae, Fuminori Sakurai, Ryosuke Ono, Rika Onishi, Kosuke Takayama, Hiroyuki Mizuguchi |
| Journal | The Journal of general virology (J Gen Virol) Vol. 103 Issue 6 (06 2022) ISSN: 1465-2099 [Electronic] England |
| PMID | 35731650 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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