Cai Z, Gao L, Hu K, Wang QM. Parthenolide enhances the metronomic chemotherapy effect of cyclophosphamide in lung cancer by inhibiting the NF-kB signaling pathway. World J Clin Oncol 2024; 15(7): 895-907 [PMID: 39071467 DOI: 10.5306/wjco.v15.i7.895]
Corresponding Author of This Article
Qi-Ming Wang, PhD, Doctor, Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dong Ming Road, Zhengzhou 450008, Henan Province, China. qimingwang1006@126.com
Research Domain of This Article
Cell Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Jul 24, 2024; 15(7): 895-907 Published online Jul 24, 2024. doi: 10.5306/wjco.v15.i7.895
Parthenolide enhances the metronomic chemotherapy effect of cyclophosphamide in lung cancer by inhibiting the NF-kB signaling pathway
Zheng Cai, Lang Gao, Kai Hu, Qi-Ming Wang
Zheng Cai, Qi-Ming Wang, Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, Henan Province, China
Zheng Cai, Lang Gao, Kai Hu, Department of Oncology, The No. 1 Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, Kunming 650021, Yunnan Province, China
Author contributions: Cai Z and Wang QM conceived and designed the experiments; Cai Z, Gao L, Hu K, and Wang QM performed the experiments; Cai Z and Gao L analyzed and interpreted the data; Hu K, and Wang QM contributed reagents/materials/analysis tools; Cai Z wrote original draft; Gao L, Hu K, and Wang QM reviewed and edited draft; All authors have read and agreed to the published version of the manuscript.
Supported byJoint Funding of Yunnan Ministry of Science and Technology, No. 2019FF002-048; and Beijing Heathco Clinical Oncology Research Foundation, No. Y-Q201802-048.
Institutional animal care and use committee statement: All animal experimental procedures were approved by the ethics committee of the Affiliated Hospital of Yunnan University of Traditional Chinese Medicine (Approval No. DW2022-016) and performed according to the institutional animal care guidelines.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request at qimingwang1006@126.com.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: Https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qi-Ming Wang, PhD, Doctor, Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dong Ming Road, Zhengzhou 450008, Henan Province, China. qimingwang1006@126.com
Received: February 26, 2024 Revised: May 11, 2024 Accepted: June 6, 2024 Published online: July 24, 2024 Processing time: 140 Days and 19.6 Hours
Abstract
BACKGROUND
Parthenolide (PTL), a sesquiterpene lactone derived from the medicinal herb Chrysanthemum parthenium, exhibits various biological effects by targeting NF-kB, STAT3, and other pathways. It has emerged as a promising adjunct therapy for multiple malignancies.
AIM
To evaluate the in vitro and in vivo effect of PTL on cyclophosphamide (CTX) metronomic chemotherapy.
METHODS
The cytotoxicity of PTL and CTX on Lewis lung cancer cells (LLC cells) was assessed by measuring cell activity and apoptosis. The anti-tumor efficiency was evaluated using a tumor xenograft mice model, and the survival of mice and tumor volume were monitored. Additionally, the collected tumor tissues were analyzed for tumor microenvironment indicators and inflammatory factors.
RESULTS
In vitro, PTL demonstrated a synergistic effect with CTX in inhibiting the growth of LLC cells and promoting apoptosis. In vivo, metronomic chemotherapy combined with PTL and CTX improved the survival rate of tumor-bearing mice and reduced tumor growth rate. Furthermore, metronomic chemotherapy combined with PTL and CTX reduced NF-κB activation and improved the tumor immune microenvironment by decreasing tumor angiogenesis, reducing Transforming growth factor β, and α-SMA positive cells.
CONCLUSION
PTL is an efficient compound that enhances the metronomic chemotherapy effects of CTX both in vitro and in vivo, suggesting its potential as a supplementary therapeutic strategy in metronomic chemotherapy to improve the chemotherapy effects.
Core Tip: Our present study found that as a specific inhibitor of NF-kB, Parthenolide can promote the efficiency of cyclophosphamide in lung cancer via inhibiting NF-kB signaling in vitro and in vivo. Our present study will help scientists and clinicians to draw up novel rhythmic chemotherapy strategies.
