PMID- 29483938 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220316 IS - 1749-8546 (Print) IS - 1749-8546 (Electronic) IS - 1749-8546 (Linking) VI - 13 DP - 2018 TI - Ginsenoside G-Rh2 synergizes with SMI-4a in anti-melanoma activity through autophagic cell death. PG - 11 LID - 10.1186/s13020-018-0168-y [doi] LID - 11 AB - 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. FAU - Lv, Da-Lun AU - Lv DL AD - 1Department of Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu, 241000 Anhui China. GRID: grid.452929.1 FAU - Chen, Lei AU - Chen L AD - 1Department of Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu, 241000 Anhui China. GRID: grid.452929.1 FAU - Ding, Wei AU - Ding W AD - 1Department of Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu, 241000 Anhui China. GRID: grid.452929.1 FAU - Zhang, Wei AU - Zhang W AD - 1Department of Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu, 241000 Anhui China. GRID: grid.452929.1 FAU - Wang, He-Li AU - Wang HL AD - 1Department of Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu, 241000 Anhui China. GRID: grid.452929.1 FAU - Wang, Shuai AU - Wang S AD - 1Department of Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu, 241000 Anhui China. GRID: grid.452929.1 FAU - Liu, Wen-Bei AU - Liu WB AUID- ORCID: 0000-0002-1437-3102 AD - 2Dermatological Department, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu, 241000 Anhui China. GRID: grid.452929.1 LA - eng PT - Journal Article DEP - 20180221 PL - England TA - Chin Med JT - Chinese medicine JID - 101265109 PMC - PMC5820787 OTO - NOTNLM OT - Apoptosis OT - Autophagy OT - G-Rh2 OT - Melanoma OT - SMI-4a EDAT- 2018/02/28 06:00 MHDA- 2018/02/28 06:01 PMCR- 2018/02/21 CRDT- 2018/02/28 06:00 PHST- 2018/01/15 00:00 [received] PHST- 2018/02/12 00:00 [accepted] PHST- 2018/02/28 06:00 [entrez] PHST- 2018/02/28 06:00 [pubmed] PHST- 2018/02/28 06:01 [medline] PHST- 2018/02/21 00:00 [pmc-release] AID - 168 [pii] AID - 10.1186/s13020-018-0168-y [doi] PST - epublish SO - Chin Med. 2018 Feb 21;13:11. doi: 10.1186/s13020-018-0168-y. eCollection 2018.