Melittin induces NSCLC apoptosis via inhibition of miR-183
Authors Gao D, Zhang J, Bai L, Li F, Dong Y, Li Q
Received 31 March 2018
Accepted for publication 1 June 2018
Published 1 August 2018 Volume 2018:11 Pages 4511—4523
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 2
Editor who approved publication: Dr Samir Farghaly
Dongqi Gao, Jingjing Zhang, Lu Bai, Fubo Li, Yi Dong, Qingshan Li
Department of Oncology, Affiliated Hospital of Chengde Medical University, Chengde 067000, China
Background: Non-small-cell lung cancer (NSCLC) has one of the highest mortality rates among cancers worldwide, with a poor prognosis. Previous studies have reported that melittin, an active component of apitoxin, exerts anti-inflammatory and antitumor effects via vascular endothelial growth factor or FoxO1.
Methods: CCK8, flow cytometry assay and Western blotting were performed to evaluate the effect of melittin on NSCLC.
Results: The present study demonstrates that melittin activated caspase-2 by inhibiting miR-183 expression and, thus, induced NSCLC apoptosis in both NCI-H441 cancer cell line assays and an in vivo xenograft model. The results of the cell-based assays showed that melittin (2 µg/mL) robustly suppressed miR-183 expression level and resulted in decreased invasion and migration abilities of NCI-H441 cells. Additionally, a flow cytometry assay and Western blotting showed that melittin induced NSCLC NCI-H441 cell apoptosis along with significant elevation of caspase-2 and Bax, which are regulators of cell apoptosis, and reduced Bcl-2 protein expression compared with dimethyl sulfoxide control. Furthermore, subcutaneous injection of melittin (5 mg/kg) significantly suppressed NSCLC tumor growth compared with vehicle group tumors, determined through tumor size and weight.
Conclusion: Taken together, the aforementioned findings contribute to identification of a novel therapeutic target in the treatment of NSCLC, in patients diagnosed with a high expression of miR-183. Moreover, this article provides solid evidence for the inhibitory effect of melittin on NSCLC cancer cell growth.
Keywords: miR-183, melittin, NSCLC, caspase 2, apoptosis
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