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Chinese Medicine
Published in: Chinese Medicine 1/2018

Open Access 01-12-2018 | Research

Ginsenoside G-Rh2 synergizes with SMI-4a in anti-melanoma activity through autophagic cell death

Authors: Da-lun Lv, Lei Chen, Wei Ding, Wei Zhang, He–li Wang, Shuai Wang, Wen-bei Liu

Published in: Chinese Medicine | Issue 1/2018

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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.
Appendix
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Metadata
Title
Ginsenoside G-Rh2 synergizes with SMI-4a in anti-melanoma activity through autophagic cell death
Authors
Da-lun Lv
Lei Chen
Wei Ding
Wei Zhang
He–li Wang
Shuai Wang
Wen-bei Liu
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2018
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/s13020-018-0168-y

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