Effects and Mechanisms of Novel Sedative "Remimazolam Besylate" on Cancer Cell Biology

Abstract

Surgical resection is the primary treatment for most solid cancers. Although the surgery effectively removes tumours, secondary tumours, including local recurrence or metastasis in distant organs, often occur due to various factors, such as the surgical stress response and anaesthetic drugs or techniques that may influence cancer cell biology and immune function during the perioperative period. Remimazolam besylate is a novel sedative characterised by its ultra-short-acting effects and rapid onset. It has recently been introduced for procedural sedation and anaesthesia maintenance use. However, its impact on cancer and postoperative oncological outcomes has not been thoroughly investigated. Therefore, the current thesis aims to examine its effects and underlying mechanisms on cancer cell biology with in vitro cultures of human lung carcinoma, prostate cancer, and colorectal cancer together with a xenograft model of human lung cancer. Remimazolam besylate inhibited the proliferation and migration of human lung carcinoma and prostate cancer cells and induced apoptosis in a dose-dependent manner. Furthermore, it also suppressed the proliferation and migration of colorectal cancer cells, caused apoptotic death in a dose- and time-dependent manner. Its apoptotic effect was mediated through the activation of endoplasmic reticulum stress, as evidenced by the upregulation of the PERK, p-EIF2α, ATF4, and CHOP signallings. Furthermore, a relevant clinical dosage of remimazolam besylate significantly reduced the tumour size of human lung carcinoma in a xenograft model. The data presented in the current thesis suggest that a novel sedative, remimazolam besylate, possesses anti-cancer properties. These findings may have significant clinical implications as it may be an alternative to general inhalational anaesthetics potentially reducing the risk of cancer recurrence and metastasis in cancer patients following surgery. Nevertheless, clinical trials are required to further assess the effects of remimazolam besylate on oncological outcomes.