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Liver X receptor (LXR) agonists inhibit various types of tumor growth and have been applied to preclinical research. In colon cancer cells, LXR agonists induce pyroptotic cell death through the predominant cytoplasmic localisation of LXRβ. In the present study, we determined whether tumor cell death induced by LXR agonists in colon cancer cells could elicit immunogenic cell death (ICD). LXR agonist-treated-colon cancer cells exhibited translocation of calreticulin (CRT) and release of HMGB1 and ATP into the medium. Expression levels of CRT and HMGB1 were also increased in T0901317-treated Balb/c mice. Furthermore, compared with control mice, mice vaccinated with T0901317-treated CT26 cells showed reduced tumor volumes and protection against a challenge with live tumor cells. Inhibition of CRT or HMGB1 expression in CT26 cells abolished this protection in Balb/c mice. In conclusion, the LXR agonist T0901317 induces ICD in colon cancer cells. CRT exposure and HMGB1 release play a critical role in the immunogenicity of this treatment.

Liver X receptors (LXRs) are involved in various diseases associated with lipid disorders, and in regulating cancer cell proliferation. However, the underlying molecular mechanisms, especially those in gastric cancer (GC) remain to be clarified. In this study, immunohistochemistry analysis revealed that LXRβ was mainly expressed in GC tissue, with less expression in adjacent normal tissues. The LXRβ agonist T0901317 efficiently suppressed the proliferation and colony formation of various GC cell lines. We further showed that LXRβ translocated from the cytoplasm to the nucleus when activated by T0901317. LXRβ nuclear localization suppressed the activation of Wnt signalling and decreased the expression of target genes such as MYC, BMP4, and MMP7 through binding to their promoters. Moreover, we demonstrated that the LXR agonist efficiently suppressed GC tumour growth in a nude mouse xenograft model. Taken together, these results revealed that LXRβ agonist inhibited GC cells proliferation by suppressing Wnt signalling via LXRβ relocalization. The results strongly suggest that LXRβ could be a promising target in GC therapy.

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