Blocking integrin αVβ3 makes brain tumor cells more sensitive to temozolomide by reducing DNA repair

Knockdown of integrin β3 increased sensitivity of high-grade glioma cells to temozolomide-induced cytotoxicity.

• Inhibition of integrin β3 led to the suppression of the FAK/Src/Akt/NFκB signaling pathway.
• Silencing integrin β3 resulted in the degradation of Rad51 and reduced repair of DNA double-strand breaks.
• Down-regulation of β3 did not further sensitize Rad51 knockdown cells to temozolomide, indicating a direct relationship.
• In β3-silenced cells exposed to temozolomide, cleavage of anti-apoptotic proteins and activation of caspases were observed.
• Increased γH2AX foci formation and altered NFκB signaling were confirmed in mouse glioma xenografts treated with the integrin inhibitor and temozolomide.

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