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Inhibition of autophagy enhances SMI-4a-induced growth inhibition and apoptosis of melanoma cells.
- Source :
-
Tropical Journal of Pharmaceutical Research . Mar2018, Vol. 17 Issue 3, p401-407. 7p. - Publication Year :
- 2018
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15965996
- Volume :
- 17
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Tropical Journal of Pharmaceutical Research
- Publication Type :
- Academic Journal
- Accession number :
- 129125170
- Full Text :
- https://doi.org/10.4314/tjpr.v17i3.3