Anti-tumor Effects of Curcumin and ABT-737 in Combination Therapy for Glioblastoma in Vivo.

Abstract

The resistance of tumor cells to ABT-737 can be attributed to alterations in the equilibrium of Bcl-2 family proteins. In this study, the effect of curcumin on the Mcl-1expression and the sensitivity of glioblastoma cells to ABT-737 were examined. Trypan blue assay and colony formation assay were performed to explore the effects of treatments on cell proliferation. MTT assay was performed to measure cytotoxicity. Cell migration was determined using a wound healing assay. Cell apoptosis was measured by Hoechst 33342 staining, ELISA cell death, and caspase-3 activity assay. The expression levels of Mcl-1 mRNA were also tested by qRT-PCR. Our results revealed that combination therapy significantly lowered the IC₅₀ value and synergistically decreased the colony formation and migration, cell survival and growth of glioblastoma cells compared with curcumin or ABT-737 alone. Treatment with curcumin clearly inhibited the expression of Mcl-1 mRNA. Moreover, suppression of Mcl-1 mRNA by curcumin was associated with enhancement of apoptosis induced by ABT-737. In conclusion, curcumin has the ability to inhibit the cell proliferation and migration, and activate the intrinsic pathway of apoptosis. Moreover, it can enhance the sensitivity of glioblastoma cells to ABT-737 by suppressing the expression of Mcl-1.