Thymoquinone and pentoxifylline enhance the chemotherapeutic effect of cisplatin by targeting Notch signaling pathway in mice.

摘要: Abstract Aims Notch signaling is highly implicated in several cancers and chemoresistance. Therefore, Notch-targeted therapies might be beneficial enhancing chemotherapeutic effect cancer regression. This study aimed to investigate implication of development progression solid Ehrlich carcinoma (SEC) enhancement anticancer cisplatin (CIS) by addition thymoquinone (TQ) pentoxifylline (PTX) through modulation Notch. Main methods SEC was induced mice as model for mammary s.c. injection 1 × 106 cells into back the mice. On 12th day, tumor developed were divided seven groups; control, early CIS (ECIS), ECIS + ETQ, ECIS + ETQ + EPTX, late (LCIS), LCIS + LTQ, LCIS + LTQ + LPTX. Early treatment started on whereas begun 19th day from inoculation. At endpoint, samples collected detection Notch1, Hes1, Jagged1, β-catenin, TNF-α, IL-6, IFN-γ, IL-2, VEGF, apoptosis, CD4, CD8. Key findings Adding PTX TQ significantly reduced VEGF with increment CD8, apoptotic cells. Moreover, treated groups showed remarkable attenuation growth relevant parameters compared their counterpart later groups. Significance Addition a synergistic action better oncostatic mainly suppression. Consequently, shutting could great interest promoting chemosensetivity control.