Dexmedetomidine provides type-specific tumour suppression without tumour-enhancing effects in syngeneic murine models

Abstract

Background: Dexmedetomidine is a widely used anaesthetic adjuvant for cancer resection surgeries. However, recent reports suggest that it may promote tumour growth or metastasis, so it is essential to clarify its tumour-related effects.

Methods: Seven syngeneic murine tumour models were used to assess the impact of dexmedetomidine on primary tumour growth, spontaneous tumour metastasis, and surgical resection-associated metastasis. Cancer cell proliferation and apoptosis experiments, terminal deoxynucleotidyl transferase dUTP nick-end labelling assays, immune cell analysis, specific T-cell depletion experiments, and gene transcription analysis were conducted to identify the underlying mechanisms.

Results: Dexmedetomidine did not affect growth of EO771 or 4T1 breast tumours, LAP0297 or LLC lung tumours, MCA205 fibrosarcoma, or their spontaneous lung metastases. It did not promote lung metastasis after breast cancer resection. Dexmedetomidine significantly suppressed MCA38 and CT26 colorectal tumour growth (P<0.01) and promoted apoptosis in MCA38 tumour tissues (P<0.05) without affecting proliferation and apoptosis of MCA38 tumour cells in vitro, suggesting indirect anti-tumour effects. Dexmedetomidine increased the proportions of intratumour CD4⁺ T (P<0.01), CD8⁺ T (P<0.001), and natural killer cells (P<0.01), and it upregulated transcription of the cytotoxicity-related genes Infg, Tnfa, and Cxcl9 (P<0.05) in MCA38 tumours. Either CD8⁺ or CD4⁺ T-cell depletion reversed the anti-tumour effects of dexmedetomidine on MCA38 tumours (P<0.05).

Conclusions: Dexmedetomidine conferred colorectal tumour-type specific suppression by modulation of tumour CD4⁺ and CD8⁺ T cells without tumour-enhancing effects.

Keywords: T cells; colorectal cancer; dexmedetomidine; metastasis; tumour microenvironment; tumour progression.