2. Academic Validation
  3. Oridonin combined with cisplatin synergistically induces apoptosis by activating the NOXA-BCL2 axis in esophageal squamous cell carcinoma

Oridonin combined with cisplatin synergistically induces apoptosis by activating the NOXA-BCL2 axis in esophageal squamous cell carcinoma

  • Biochem Pharmacol. 2025 Jul:237:116953. doi: 10.1016/j.bcp.2025.116953.
Qihang Guo 1,  Yue Mao 2,  Jiyu Zhang 1,  Yangyang Zhou 3,  Yue Zhao 1,  Ying Li 1,  Jinglong Lv 1,  Huiyu Yang 4,  Bingrong Liu 5
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450052 Henan, China.
  • 2 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450052 Henan, China; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052 Henan, China.
  • 3 Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000 Hubei, China.
  • 4 Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450052 Henan, China. Electronic address: huiyuyang@126.com.
  • 5 Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 Henan, China; State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450052 Henan, China. Electronic address: fccliubr@zzu.edu.cn.
PMID: 40250733 DOI: 10.1016/j.bcp.2025.116953
Abstract

Esophageal Cancer, a malignant neoplasm originating from the epithelial cells of the esophagus, predominantly manifests as esophageal squamous cell carcinoma (ESCC) in approximately 90% of cases in China. Cisplatin-based chemotherapy regimens remain the first-line therapeutic option for ESCC, however, the five-year overall survival rate of patients is disappointingly low. Oridonin, a bioactive diterpenoid extracted from the traditional Chinese medicine herb Donglingcao, has demonstrated inhibitory effects against various malignancies. Currently, research on the combination of oridonin and cisplatin for the treatment of ESCC is limited. This study aims to elucidate the potential synergistic anti-cancer effects of oridonin in combination with cisplatin on ESCC, along with the underlying synergistic molecular mechanisms. In vitro experiments revealed that the combination of oridonin and cisplatin could synergistically inhibit ESCC cell proliferation, migration, invasion. The synergistic effect also induced cell cycle arrest and promoted Apoptosis via the mitochondrial pathway by augmenting NOXA transcriptional activity and activating the NOXA-BCL2 axis. In vivo experiments corroborated these findings, showing a marked reduction in the growth of subcutaneous xenograft tumors in mice treated with the combination, without exacerbating the cisplatin-associated side effects such as weight loss or hepatic and renal toxicity. In conclusion, the combination of oridonin and cisplatin can synergistically inhibit the development of ESCC through the activation of the NOXA-BCL2 axis signaling pathway. This treatment is both safe and effective,presenting a promising prospect for combined therapeutic application in ESCC management.

Keywords

Cisplatin; Esophageal squamous cell carcinoma; Induce apoptosis; Oridonin; Synergistic effect.

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