Exploring apoptotic pathways in SH-SY5Y neuroblastoma cells: combined effects of napabucasin and doxorubicin

Background: Neuroblastoma often begins in infancy and is one of the most common types of cancer among children. Napabucasin (NP) (BBI608), a natural naphthoquinone emerging as a novel inhibitor of STAT3, has been found to effectively kill cancer stem-like tumour cells. However, the effect of napabucasin on SH-SY5Y cells is currently unclear. The aim of this study was to investigate the effects and mechanisms of NP and doxorubicin (DX) on human metastatic neuroblastoma cells. Materials and methods: In this study, human neuroblastoma cells line (SHSY--5Y) were used. Apoptotic activation of NP and DX via the Bcl-2/Bax signalling pathway was evaluated by qRT-PCR, Western blotting and Tali cytometry. It was also detected by MTT, a cell viability test. Results: NP and DX antiproliferatively and invasively affected SH-SY5Y cells. Additionally, NP induced apoptosis by pausing the cell cycle. Moreover, NP treatment inhibited the expression of Bcl-2, which is associated with apoptosis, while it clearly inhibited the expression of Bax and CASP3 genes. Conclusions: Our results show that NP and DX suppress the proliferation of neuroblastoma cells and could do this through apoptotic pathways. NP can be used to suppress metastasis of SHSY-5Y cells as an inhibitor of the apoptosis pathway Bcl-2. We suggest that NP, which provides tumour suppression through an apoptotic mechanism, may be an alternative treatment agent in neurological cancers such as neuroblastoma. (Folia Morphol 2025; 84, 3: 544-552)