Anti-Cancer treatments affecting PI3K/Akt/Mtor and Ras/MAPK pathways in neuroblastoma

Abstract

BACKGROUND In this study, we applied combination therapy of RA and Tac to NB cells with different molecular properties and aimed to evaluate its effects on proliferation, differentiation, and apoptotic pathways in NB. METHODS Four cell lines of different characteristics; (KELLY, LAN-5, CHP-134, and SHSY5Y) were cultured and treated with various doses of RA and Tac. The IC50 values were determined by through WST analysis. The IC50 of the RA+Tac combination was applied to the cells. To determine the apoptosis/necrosis rate, the cells were dyed with Annexin V/PI. To examine the protein levels of certain pathways, Western Blot and IHC were performed. RESULTS The RA and RA+Tac treatments demonstrated beneficial effects in all the NB cell lines. The combination of RA+Tac treatments is relatively more efficient than RA in promoting apoptosis, inhibiting proliferation, and decreasing the expression levels of signal pathway proteins (p < 0.05). Only the Tac treatment did not have a significant effect on the NB cells. In low doses and in combination with RA, Tac was found to be effective on cells. CONCLUSION In summary, the NB cells differentiated with the RA treatment were more responsive when RA+Tac was administered. Tac exhibited a synergistic effect combined with RA and affected the crucial signal pathway proteins. Our studies lead to a more comprehensive study of the combination of RA and Tac.

Keywords

• Neuroblastoma
• retinoic acid
• signal pathways
• treatment of neuroblastoma
• tacrolimus

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