Inhibiting the Src/STAT3 signaling pathway contributes to the anti‑melanoma mechanisms of dioscin

Liu,Yu‑Xi; Xu,Bo‑Wen; Chen,Ying‑Jie; Fu,Xiu‑Qiong; Zhu,Pei‑Li; Bai,Jing‑Xuan; Chou,Ji‑Yao; Yin,Cheng‑Le; Li,Jun‑Kui; Wang,Ya‑Ping; Wu,Jia‑Ying; Wu,Ying; Chan,Kam‑Kwan; Liang,Chun; Yu,Zhi‑Ling

doi:10.3892/ol.2020.11315

Inhibiting the Src/STAT3 signaling pathway contributes to the anti‑melanoma mechanisms of dioscin

Authors:
- Yu‑Xi Liu
- Bo‑Wen Xu
- Ying‑Jie Chen
- Xiu‑Qiong Fu
- Pei‑Li Zhu
- Jing‑Xuan Bai
- Ji‑Yao Chou
- Cheng‑Le Yin
- Jun‑Kui Li
- Ya‑Ping Wang
- Jia‑Ying Wu
- Ying Wu
- Kam‑Kwan Chan
- Chun Liang
- Zhi‑Ling Yu
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Affiliations: School of Chinese Medicine, Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Kowloon 999077, Hong Kong, SAR, P.R. China, Enzynomics Limited, Guangzhou, Guangdong 510000, P.R. China
Published online on: January 17, 2020 https://doi.org/10.3892/ol.2020.11315
Pages: 2508-2514

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Abstract

Late stage melanoma is associated with a high mortality rate. Signal transducer and activator of transcription 3 (STAT3) is currently a target for melanoma treatment as it is constitutively activated with high frequency in melanoma. Dioscin is a natural steroid saponin that is present in several medical herbs. A previous study demonstrated that dioscin inhibits STAT3 signaling in a cerebral ischemia‑reperfusion injury rat model. Furthermore, dioscin has been reported to exert anti‑melanoma effects in B16 melanoma cells and a B16 allograft mouse model. The present study investigated whether inhibition of STAT3 signaling is involved in the anti‑melanoma effects of dioscin. The results of the present study demonstrated that dioscin significantly decreased viability, induced apoptosis and suppressed migration of human A375 melanoma cells and murine B16F10 melanoma cells. Furthermore, dioscin inhibited the phosphorylation of STAT3 and Src (an upstream kinase of STAT3), and downregulated mRNA levels of STAT3‑targeted genes, including B‑cell lymphoma‑2, cyclin D1 and matrix metalloproteinase‑2. In addition, overexpression of STAT3 decreased the anti‑proliferative effects of dioscin. Overall, the results of the present study indicate that inhibiting the Src/STAT3 signaling pathway contributes to the anti‑melanoma molecular mechanisms of dioscin. These results provide further pharmacological groundwork for developing dioscin as a novel anti‑melanoma agent.

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