loading page

Combined hesperetin and cisplatin synergistically inhibit lung cancer associated with Nrf2 signaling pathways and oxidative stress
  • +2
  • Hui Wang,
  • Yibin Liu,
  • Han Chen,
  • Shijie Wei,
  • Hua Gao
Hui Wang
General Hospital of Ningxia Medical University
Author Profile
Yibin Liu
General Hospital of Ningxia Medical University
Author Profile
Han Chen
Affiliated Hospital of Xi’an Medical University
Author Profile
Shijie Wei
General Hospital of Ningxia Medical University
Author Profile
Hua Gao
General Hospital of Ningxia Medical University

Corresponding Author:[email protected]

Author Profile

Abstract

Abstract Objective: Lung cancer (LC) is well known for its high morbidity and mortality rates. The primary objective of this study was to investigate the synergistic effects of hesperetin (HES), a bioactive compound found in sweet oranges, in combination with cisplatin (CDDP), on LC treatment. Methods: Human A549 and mouse Lewis lung cancer (LLC) cell lines were treated with HES, CDDP, or their combination. Cell viability was assessed using CCK-8 assays. Western blotting evaluated Nrf2 pathway modulation. In vivo, LLC xenografts in C57BL/6 mice assessed tumor growth and kidney function. Results: The combination of HES with CDDP synergistically inhibited lung cancer cell viability in A549 and LLC cells compared to individual treatments (P < 0.05). This synergistic effect was associated with reduced Nrf2 pathway activation, enhancing oxidative stress sensitivity induced by CDDP. In vivo, HES + CDDP treatment significantly suppressed tumor growth in LLC xenograft mice, accompanied by alleviated CDDP-induced kidney injury, indicated by improved histopathology, reduced apoptosis, and restored antioxidant enzyme levels in kidney tissues. Conclusions: Combining HES with CDDP enhances LC treatment efficacy by synergistically inhibiting tumor growth and modulating the Nrf2 pathway. Additionally, HES protects against CDDP-induced kidney injury, suggesting potential benefits in LC treatment strategies.
19 Jul 2024Submitted to Cancer Reports
07 Aug 2024Submission Checks Completed
07 Aug 2024Assigned to Editor
07 Aug 2024Review(s) Completed, Editorial Evaluation Pending
10 Aug 2024Reviewer(s) Assigned
11 Oct 2024Editorial Decision: Revise Major