Zeng Haiyan, Guo Aoxiang, Liu Zhenyang, Xiang Shijian, Zheng Fanghao
Department of Clinical Laboratory, Shenzhen Guangming District People's Hospital, Shenzhen, 518106, China.
Department of Pharmacy, Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China.
Med Oncol. 2025 Mar 19;42(4):118. doi: 10.1007/s12032-025-02666-9.
Isoliquiritigenin (ISL) has been reported with antitumor activities. While, the underlying molecular mechanisms remain largely unknown. The transcription factor of programmed cell death ligand 1 (PD-L1), STAT3, plays an important role in tumor metastasis. In this study, we first verified that ISL suppressed the growth and metastasis ability of melanoma cells both in vitro and in vivo. Then, we found that ISL could repress the expression of PD-L1 and STAT3 phosphorylation. TIMER algorithm analysis showed that the levels of immune infiltration were positively correlated with the expression of STAT3. Furthermore, the STAT3 phosphorylation inhibitor Stattic could enhance the effect of ISL in suppressing cell proliferation, promoting apoptosis, and restraining the ability of migration and invasion of melanoma cells. This study revealed that ISL inhibited melanoma metastasis and repressed PD-L1 expression by repressing the phosphorylation of STAT3, which help us to understand the mechanism of ISL in melanoma therapy.
异甘草素（ISL）已被报道具有抗肿瘤活性。然而，其潜在的分子机制仍 largely 未知。程序性细胞死亡配体 1（PD-L1）的转录因子 STAT3 在肿瘤转移中起重要作用。在本研究中，我们首先证实 ISL 在体外和体内均抑制黑色素瘤细胞的生长和转移能力。然后，我们发现 ISL 可抑制 PD-L1 的表达和 STAT3 的磷酸化。TIMER 算法分析表明免疫浸润水平与 STAT3 的表达呈正相关。此外，STAT3 磷酸化抑制剂 Stattic 可增强 ISL 在抑制细胞增殖、促进凋亡以及抑制黑色素瘤细胞迁移和侵袭能力方面的作用。本研究揭示 ISL 通过抑制 STAT3 的磷酸化来抑制黑色素瘤转移并抑制 PD-L1 表达，这有助于我们了解 ISL 在黑色素瘤治疗中的机制。
