Natural product Eriocalyxin B exerts anti-tumor effects by downregulating TCEA3 expression and sensitizes immune checkpoint blockade therapy in osteosarcoma.

Abstract

Osteosarcoma (OS) remains the most common bone tumor and the prognosis for many patients remains stagnant due to the unsatisfactory therapeutic effect of conventional treatment regimens. This research explored the effect and mechanism of a novel natural product, Eriocalyxin B (EB), in pathogenesis and immunotherapy in OS. Cell Count Kit 8 assay, colony formation assay, and wound healing assay were employed to detect the proliferative, colony-forming, and migratory abilities of human OS cells following EB treatment. Moreover, xenograft growth assay was performed to assess the effect of EB on OS in vivo. Subcutaneous OS models constructed in immunocompetent mice were employed to evaluate the effect of EB treatment in combination with immune checkpoint blockades (ICBs) PD1ab and CTLA4ab. Immunohistochemistry (IHC) staining was utilized to detect the level of CD8+ T cells infiltration and Ki67 expression. TARGET database, RNA interference technology, and qPCR assay were employed to explore the mechanism of EB on OS. EB inhibited the proliferative, colony-forming, and migratory abilities of the human OS cells MG63 and U2OS both in vitro and in vivo. TARGET data analysis demonstrated that up-regulation of TCEA3 was significantly negatively correlated with overall survival in OS patients. EB exerted anti-tumor activity via downregulation of TCEA3. EB, in conjunction with ICBs, synergistically optimized anti-tumorigenic activity against OS in immunocompetent mice. EB may promote infiltration of CD8+ T cells and down-regulate Ki67 expression. These results signaled that EB may have a role as a candidate therapeutic or preventive agent for the treatment of OS.