Open Access

ARTICLE

Melittin inhibited glycolysis and induced cell apoptosis in cisplatinresistant lung adenocarcinoma cells via TRIM8

by Sufang Zhang^1,2,#, Xiang Lv^1,#, Li Li^3,#, Yingbin Luo¹, Huinan Xiang¹, Lixin Wang^2,*, Yan Li^1,*

1 Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China
2 Department of Traditional Chinese and Western Medicine, Shanghai pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China
3 Department of Respiratory Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China

* Address correspondence to: Lixin Wang, ; Yan Li,
# These authors contributed equally to this study

BIOCELL 2021, 45(1), 167-175. https://doi.org/10.32604/biocell.2021.013636

Received 14 August 2020; Accepted 25 September 2020; Issue published 26 January 2021

Abstract

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.

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