Corynoline inhibits esophageal squamous cell carcinoma growth via targeting Pim-3.

Yunshu Shi, Qiang Yuan, Yingying Chen, Xiaoyu Li, Yujuan Zhou, Hao Zhou, Feng Peng, Yanan Jiang, Yan Qiao, Jimin Zhao, Chi Zhang, Junyong Wang, Kangdong Liu, Zigang Dong

Phytomedicine : international journal of phytotherapy and phytopharmacology 2024 Jan

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Esophageal squamous cell carcinoma (ESCC) is an aggressive and deadly malignancy characterized by late-stage diagnosis, therapy resistance, and a poor 5-year survival rate. Finding novel therapeutic targets and their inhibitors for ESCC prevention and therapy is urgently needed. We investigated the proviral integration site for maloney murine leukemia virus 3 (Pim-3) protein levels using immunohistochemistry. Using Methyl Thiazolyl Tetrazolium and clone formation assay, we verified the function of Pim-3 in cell proliferation. The binding and inhibition of Pim-3 by corynoline were verified by computer docking, pull-down assay, cellular thermal shift assay, and kinase assay. Cell proliferation, Western blot, and a patient-derived xenograft tumor model were performed to elucidate the mechanism of corynoline inhibiting ESCC growth. Pim-3 was highly expressed in ESCC and played an oncogenic role. The augmentation of Pim-3 enhanced cell proliferation and tumor development by phosphorylating mitogen-activated protein kinase 1 (MAPK1) at T185 and Y187. The deletion of Pim-3 induced apoptosis with upregulated cleaved caspase-9 and lower Bcl2 associated agonist of cell death (BAD) phosphorylation at S112. Additionally, binding assays demonstrated corynoline directly bound with Pim-3, inhibiting its activity, and suppressing ESCC growth. Our findings suggest that Pim-3 promotes ESCC progression. Corynoline inhibits ESCC progression through targeting Pim-3. Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.

Citation

Yunshu Shi, Qiang Yuan, Yingying Chen, Xiaoyu Li, Yujuan Zhou, Hao Zhou, Feng Peng, Yanan Jiang, Yan Qiao, Jimin Zhao, Chi Zhang, Junyong Wang, Kangdong Liu, Zigang Dong. Corynoline inhibits esophageal squamous cell carcinoma growth via targeting Pim-3. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024 Jan;123:155235