Abstract | BACKGROUND:
Melanoma is a leading cause of cancer death worldwide, and SMI-4a and G-Rh2 exert anti- tumor activity in multiple cancer. However, SMI-4a as well as a synergistic relationship between SMI-4a and G-Rh2 in anti- melanoma capacity are still unknown. Therefore, we investigated the effects of SMI-4a and combined SMI-4a with G-Rh2 on the viability, apoptosis and autophagy of melanoma, and to preliminarily explore the underlying mechanism of SMI-4a and combined SMI-4a with G-Rh2 in inhibiting tumor growth. METHODS: Cell viability was examined with cell counting Kit 8 assay and colony formation assay; Apoptosis was evaluated by flow cytometry and Caspase 3/7 activity assay; Western blotting was used to test proteins related to autophagy and the AKT/ mammalian target of rapamycin (mTOR) signaling pathway; Tumor xenograft model in BALB/c nude mice was performed to evaluate the effects of SMI-4a and combined SMI-4a with G-Rh2 in anti- melanoma in vivo. RESULTS: SMI-4a, a pharmacological inhibitor of PIM-1, could decrease cell viability, induce apoptosis, and promote Caspase 3/7 activity in both A375 and G361 melanoma cells, and SMI-4a inhibited tumor growth by inducing autophagy via down-regulating AKT/mTOR axis in melanoma cells. Furthermore, G-Rh2 amplified the anti- tumor activity of SMI-4a in melanoma cells via strengthening autophagy. CONCLUSIONS: Our results suggested that SMI-4a could enhance autophagy-inducing apoptosis by inhibiting AKT/mTOR signaling pathway in melanoma cells, and G-Rh2 could enhance the effects of SMI-4a against melanoma cancer via amplifying autophagy induction. This study demonstrates that combined SMI-4a and G-Rh2 might be a novel alternative strategy for melanoma treatment.
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Authors | Da-Lun Lv, Lei Chen, Wei Ding, Wei Zhang, He-Li Wang, Shuai Wang, Wen-Bei Liu |
Journal | Chinese medicine
(Chin Med)
Vol. 13
Pg. 11
( 2018)
ISSN: 1749-8546 [Print] England |
PMID | 29483938
(Publication Type: Journal Article)
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