Osteosarcoma is the most prevalent
bone cancer, and
chemotherapy is still an indispensable treatment in its clinical practice.
Cisplatin (CDDP) has become the most commonly used agent for
osteosarcoma, although the outcomes of CDDP
chemotherapy remain unsatisfactory because of frequent resistance. Here, we report on a promising combination
therapy where
curcumol, a bioactive
sesquiterpenoid, enhanced CDDP-induced apoptosis to eradicate
osteosarcoma cells, and revealed that M2-like macrophages might be the underlying associated mechanisms. First, we observed that
curcumol enhanced the CDDP-mediated inhibition of cell proliferation and augmented the apoptosis in
osteosarcoma cell lines.
Curcumol contributed to preventing the migration of
osteosarcoma cells when combined with CDDP. Moreover, this
drug combination showed more potent
tumor-growth suppression in the orthotopic
transplantation of
osteosarcoma K7M2 WT cells. We then estimated
chemotherapy-associated drug-resistant genes, including ABCB1, ABCC1 and ABCG2, and found that
curcumol significantly reversed the
mRNA levels of CDDP-induced ABCB1, ABCC1 and ABCG2 genes in the
tumor tissue. Moreover, M2-like macrophages were enriched in
osteosarcoma tissues, and were largely decreased after
curcumol and CDDP treatment. Taken together, these findings suggest that
curcumol inhibits the polarization of M2-like macrophages and could be a promising combination strategy to synergize with CDDP in the
osteosarcoma.