Abstract
BackgroundMelanoma 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.MethodsCell 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.ResultsSMI-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.ConclusionsOur 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.
Highlights
Melanoma is a leading cause of cancer death worldwide, and SMI-4a and Ginsenoside Rh2 (G-Rh2) exert anti-tumor activ‐ ity in multiple cancer
SMI‐4a suppressed cell growth in melanoma cells To investigate the effect of SMI-4a on the inhibition of human melanoma cell growth, A375 and G361 cells were cultured with various concentrations of SMI-4a for 24, 48 and 72 h, respectively
These results suggest that AKT/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in SMI-4a triggered autophagy in melanoma cells
Summary
Melanoma is a leading cause of cancer death worldwide, and SMI-4a and G-Rh2 exert anti-tumor activ‐ ity in multiple cancer. 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. The overexpression of PIM-1 contributes to carcinogenesis by inhibiting apoptosis and promoting cell proliferation. Inhibition of PIM-1 activity is an emerging approach for cancer therapy. Lv et al Chin Med (2018) 13:11 inhibitor of PIM-1 protein and exerts anti-tumor activity in chronic myeloid leukemia cells. PIM-1 could promote melanoma cells migration and invasion [5, 6]. Whether SMI-4a is effective in melanoma has not been investigated
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