TNFα inhibitor C87 sensitizes EGFRvIII transfected glioblastoma cells to gefitinib by a concurrent blockade of TNFα signaling.

摘要: Objective: More than half of human glioblastomas show EGFR gene amplification and mutation, but inhibitors have notbeen effective in treating EGFR-positive glioblastoma patients. The mechanism behind this type primary resistance is not wellunderstood. aim study was to investigate gefitinib glioblastoma, explore ways circumvent thissignificant clinical problem. Methods: MTT method used test the cell viability after cells were treated with indicated drugs;real-time quantitative PCR included detect TNFα mRNA levels glioma tissues lines. ELISA wasintroduced measure protein culture supernatant gefitinib. Western blotwas activity change intracellular kinases drug-treated cells. Two mouse xenograft tumormodels carried out evaluate vivo effects a combination inhibitors. Results: We found that may be mediated by an adaptive pro-survival TNFα-JNK-Axl signalingaxis, high microenvironment further intensify resistance. A ofthe TNFα-specific small-molecule inhibitor C87 significantly enhanced sensitivity togefitinib vitro vivo. Conclusions: Our findings provide possible explanation for andsuggest dual blockade viable therapeutic strategy treatment patients withchemotherapy-refractory advanced glioblastoma. Cite article as: Ma L, She C, Shi Q, Yin Ji X, Wang Y, et al. TNFαinhibitor sensitizes EGFRvIII transfected bya concurrent signaling. Cancer Biol Med. 2019; 16: 606-17.doi: 10.20892/j.issn.2095-3941.2019.0011