Napabucasin Inhibits Proliferation and Migration of Glioblastoma Cells (U87) by Regulating JAK2/STAT3 Signaling Pathway

Abstract

Background and Objectives: Napabucasin (NP) was discovered as a natural compound that suppresses cancer stemness by inhibiting the signal transducer and activator of the transcription 3 (STAT3) signaling pathway. In this study, the anti-proliferative and apoptotic effects of NP and the chemotherapy agent doxorubicin (DX), a natural compound, on glioblastoma cells (U87) were investigated. Materials and Methods: In this study, the effects of NP and DX on cell viability on the glioblastoma U87 cell line were determined by MTT test. Expressions of Jak2/Stat3 genes were examined by qRT-PCR. Apoptosis was evaluated by Hoescht 33258 staining. Moreover, NP, its antagonistic–synergistic effects and IC50 doses of the combined treatment of DX were determined. Results: Napabucacin and doxorubicin were found to inhibit glioblastoma U87 cell proliferation. It was determined that NP applied in the range of 0.3–1 µM and its combination with DX killed almost all of the glioblastoma cells in 48 h of application. Additionally, it was observed that Jak2/Stat3 expressions downregulated. Conclusions: These results show that NP suppresses the proliferation of glioblastoma cells. It was shown that the combination of NP and DX can prevent invasion of the U87 cell line due to its Jak2/Stat3 inhibitory effect. Since it can suppress Jak2/Stat3, an important cancer cell proliferation pathway in glioblastoma, the combination of NP and DX can be used as an alternative treatment agent. But no synergistic effect of NP and DX on the U87 cells of the glioblastoma cell line was observed.

Keywords

• glioblastoma doxorubicin
• napabucasin
• Stat3 inhibitory
• MTT