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Chemotherapy is widely used for non-small cell lung cancer (NSCLC) patients at a late stage; however, NSCLC patients often acquire resistance to chemotherapeutic drugs, thus limiting the therapy efficacy. Melittin, a major component of bee venom, possesses anti-tumor activity in various cancer cells. Here, we examined the effects of melittin on A549/DDP cisplatin-resistant lung adenocarcinoma cells and xenografts formed from this cell line and investigated the possible target of melittin. Treatment with melittin resulted in the induction of cell apoptosis, glycolysis inhibition, and reduction of phosphorylated AKT (p-AKT) in A549/DDP cells. We also identified that tripartite motif-containing 8 (TRIM8) was a potential target of melittin. Moreover, we found that TRIM8 mRNA expression was elevated in NSCLC specimens as compared to adjacent normal tissues (N = 25) and that patients with high expression of TRIM8 had a poor prognosis for lung adenocarcinoma. The knockdown of TRIM8 had a similar effect of melittin, while overexpression of TRIM8 reversed the effects of melittin in A549/DDP cells. More importantly, we revealed that melittin enhanced cisplatin sensitivity in A549/DDP cells and tumor growth  in vivo  using a xenograft model of A549/DDP cells. In conclusion, melittin appears to be a potential chemotherapy sensitization agent in NSCLC.

Melittin inhibited glycolysis and induced cell apoptosis in cisplatin-resistant lung adenocarcinoma cells via TRIM8