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10.3390/biom16060791
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Article

Aloperine Suppresses the Tumorigenicity of Esophageal Squamous Cell Carcinoma by Targeting the AP-1/IL-6/STAT3 Signaling Axis

by
Ba-Fang Ma
1,2,
Jun-Nan Ye
1,2,
Die Bai
1,2,
Chang Ge
1,2,
Yingchao Guan
2,3,
Yang Lou
1,2,
Ya-Ping Liang
2,3,
Na Bu
4,
Wenhui Hao
2,3 and
Yasen Maimaitiyiming
1,2,5,*
1
Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China
2
Xinjiang Key Laboratory of Molecular Biology for Endemic Diseases, Xinjiang Medical University, Urumqi 830011, China
3
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China
4
Department of Pharmacy, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
5
Institute of Basic Medical Sciences, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China
*
Author to whom correspondence should be addressed.
Biomolecules 2026, 16(6), 791; https://doi.org/10.3390/biom16060791
Submission received: 6 April 2026 / Revised: 8 May 2026 / Accepted: 22 May 2026 / Published: 27 May 2026
(This article belongs to the Section Natural and Bio-derived Molecules)
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Abstract

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis, largely due to therapeutic resistance and the limited availability of effective targeted therapies. Aloperine (ALO), a natural alkaloid derived from Sophora alopecuroides L., exhibits anti-cancer properties in various tumor types; however, its therapeutic potential and underlying mechanism in ESCC remain unclear. Here, we report that ALO inhibited ESCC cell proliferation and colony formation in a dose- and time-dependent manner and induced caspase-dependent apoptosis, accompanied by loss of mitochondrial membrane potential and PARP1 cleavage. Mechanistically, ALO significantly suppressed inflammatory pathways, with IL-6 identified as a critical downregulated target. ALO inhibited IL-6 production by targeting the AP-1 transcription factor complex, as evidenced by reduced cFOS expression and suppressed cJUN phosphorylation. Consequently, ALO inhibited downstream IL-6/JAK-STAT3 signaling. Functionally, exogenous IL-6 rescued ALO-induced loss of cell viability. Notably, the combination of ALO with cisplatin exerted synergistic antitumor effects. In a syngeneic mice model, the combination therapy significantly reduced tumor growth and Ki67 expression while inducing apoptosis, as shown by increased TUNEL staining and cleaved caspase-3 expression, and further suppressing the IL-6/STAT3 axis compared with either monotherapy. Together, these findings demonstrate that ALO exerts potent anti-ESCC activity by targeting the AP-1/IL-6/STAT3 signaling axis. The synergistic efficacy of ALO with cisplatin highlights its potential as a promising therapeutic agent to overcome chemoresistance and improve outcomes in ESCC patients.
Keywords: Aloperine; esophageal squamous cell carcinoma; IL-6/STAT3 signaling; AP-1 transcription factor; apoptosis Aloperine; esophageal squamous cell carcinoma; IL-6/STAT3 signaling; AP-1 transcription factor; apoptosis

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MDPI and ACS Style

Ma, B.-F.; Ye, J.-N.; Bai, D.; Ge, C.; Guan, Y.; Lou, Y.; Liang, Y.-P.; Bu, N.; Hao, W.; Maimaitiyiming, Y. Aloperine Suppresses the Tumorigenicity of Esophageal Squamous Cell Carcinoma by Targeting the AP-1/IL-6/STAT3 Signaling Axis. Biomolecules 2026, 16, 791. https://doi.org/10.3390/biom16060791

AMA Style

Ma B-F, Ye J-N, Bai D, Ge C, Guan Y, Lou Y, Liang Y-P, Bu N, Hao W, Maimaitiyiming Y. Aloperine Suppresses the Tumorigenicity of Esophageal Squamous Cell Carcinoma by Targeting the AP-1/IL-6/STAT3 Signaling Axis. Biomolecules. 2026; 16(6):791. https://doi.org/10.3390/biom16060791

Chicago/Turabian Style

Ma, Ba-Fang, Jun-Nan Ye, Die Bai, Chang Ge, Yingchao Guan, Yang Lou, Ya-Ping Liang, Na Bu, Wenhui Hao, and Yasen Maimaitiyiming. 2026. "Aloperine Suppresses the Tumorigenicity of Esophageal Squamous Cell Carcinoma by Targeting the AP-1/IL-6/STAT3 Signaling Axis" Biomolecules 16, no. 6: 791. https://doi.org/10.3390/biom16060791

APA Style

Ma, B.-F., Ye, J.-N., Bai, D., Ge, C., Guan, Y., Lou, Y., Liang, Y.-P., Bu, N., Hao, W., & Maimaitiyiming, Y. (2026). Aloperine Suppresses the Tumorigenicity of Esophageal Squamous Cell Carcinoma by Targeting the AP-1/IL-6/STAT3 Signaling Axis. Biomolecules, 16(6), 791. https://doi.org/10.3390/biom16060791

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