Emodin inhibits benzidine‑enhanced survival and migration of upper urinary tract urothelial carcinoma cells by targeting the PKA/COX2 signaling pathway

Jin,Yanyang; Wang,Chengcai; Feng,Kun; Wang,Xiaowei; Tong,Ming; Tong,Guangquan

doi:10.3892/ijo.2024.5691

Emodin inhibits benzidine‑enhanced survival and migration of upper urinary tract urothelial carcinoma cells by targeting the PKA/COX2 signaling pathway

Authors:
- Yanyang Jin
- Chengcai Wang
- Kun Feng
- Xiaowei Wang
- Ming Tong
- Guangquan Tong
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Affiliations: Department of Urology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Urological Oncology Surgery Ward 1, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: September 12, 2024 https://doi.org/10.3892/ijo.2024.5691
Article Number: 103
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The carcinogenic effects of benzidine (BZ) on bladder cancer are well documented, but its potential for promoting upper urinary tract urothelial carcinoma (UTUC) remains unclear. The ability of emodin, a natural pharmaceutical compound, to prevent BZ‑associated UTUC has not been previously explored. To the best of our knowledge, the present study is the first to reveal that BZ significantly enhanced the survival and migration of UTUC cell lines in vitro. Furthermore, in vivo experiments demonstrated that BZ promoted an increase in the size of subcutaneous tumors in nude mice. Further investigation revealed that BZ upregulated the expression of protein kinase A (PKA) and cyclooxygenase 2 (COX2), along with downstream matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF), in UTUC cells. Moreover, BZ increased the levels of cyclic adenosine monophosphate (cAMP) and prostaglandin E2 (PGE2) in cell lysates. By contrast, emodin reduced the PKA and COX2 expression levels compared with the BZ‑treated group. Similarly, the in vivo experiments demonstrated that emodin significantly inhibited tumor growth in BZ‑pretreated nude mice, accompanied by reductions in the cAMP, PGE2, MMP9 and VEGF levels. These findings elucidated the role of BZ in promoting UTUC progression. Additionally, emodin has emerged as a novel inhibitor of BZ‑induced UTUC development through PKA/COX2 inhibition, suggesting its potential as a natural therapeutic agent against BZ‑associated UTUC.

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