Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Inhibition of autophagy enhances SMI-4a-induced growth inhibition and apoptosis of melanoma cells

Lei Chen¹, Da-lun Lv¹ , Wen-bei Liu², Wei Ding¹, Wei Zhang¹, He-li Wang¹, Shuai Wang¹

¹Department of Burns and Plastic Surgery; ²Dermatological Department, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu City, Anhui Province, 241000, China.

For correspondence:- Da-lun Lv Email: Lvdalun89@163.com

Accepted: 27 February 2018 Published: 31 March 2018

Citation: Chen L, Lv D, Liu W, Ding W, Zhang W, Wang H, et al. Inhibition of autophagy enhances SMI-4a-induced growth inhibition and apoptosis of melanoma cells. Trop J Pharm Res 2018; 17(3):401-407 doi: 10.4314/tjpr.v17i3.3

© 2018 The authors.
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Abstract

Purpose: To investigate the exact role of the proviral integration site for Moloney murine leukemia virus-1 (PIM-1) on autophagy as well as the underlying molecular mechanisms in melanoma.

Methods: mRNA expression levels in A375 and G361 human melanoma cell lines were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent (ELISA) and western blotting assays were applied to determine protein expression levels, while cell viability was evaluated using Cell Counting Kit 8 and colony formation assay. Flow cytometric analysis and caspase 3/7 activity assay were used to assess apoptosis.

Results: The results show that pharmacological inhibition of PIM-1 with its potent inhibitor (SMI-4a) suppressed cell viability and induced apoptosis in melanoma cell lines A375 and G361. SMI-4a also induced autophagy through inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) axis in melanoma cells. Furthermore, chloroquine, an inhibitor of autophagy, potentiated the SMI-4a-induced inhibition of tumour growth and promotion of apoptosis in melanoma cells in vitro and in vivo.

Conclusions: These results suggest that SMI-4a induces protective autophagy via PI3K/AKT/mTOR signaling pathway in melanoma cells. Thus, a combination of SMI-4a and an inhibitor of autophagy might be a novel approach to melanoma therapy.

Keywords: Apoptosis, Autophagy, Cell viability, Melanoma, PIM-1, SMI-4a