Cyclovirobuxine D inhibits growth and progression of non-small cell lung cancer cells by suppressing the KIF11-CDC25C-CDK1-CyclinB1 G2/M phase transition regulatory network and the NFκB/JNK signaling pathway

Sep 24, 2026

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Non-small cell lung cancer remains a leading cause of cancer-related death, with low 5-year overall survival and many patients diagnosed at advanced stages where resistance to conventional chemotherapy limits outcomes. Cyclovirobuxine D (CVB-D), a natural steroidal alkaloid used in Traditional Chinese Medicine, shows reported antitumor activity. This study evaluates CVB-D therapeutic effects in NSCLC using in vivo xenograft models and in vitro assays, linking antitumor efficacy to disruption of the KIF11-CDC25C-CDK1-CyclinB1 G2/M transition network and NFκB/JNK signaling.

LanguageEnglish

CategoryHealthcare

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Pages21

Reading Time53 min

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Abstract

Introduction

Background: NSCLC burden and treatment limits

Rationale for targeting KIF11

Rationale for natural plant compound context

Mechanistic focus and study aim

INTERNATIONAL JOURNAL OF ONCOLOGY 62: 57, 2023 Cyclovirobuxine D inhibits growth and progression of non‑small cell lung cancer cells by suppressing the KIF11‑CDC25C‑CDK1‑ CyclinB1 G2/M phase transition regulatory network and the NFκB/JNK signaling pathway TING XUE 1 , YAODONG CHEN2 , JIA XU3 , WEIQIN DU4 , PENGZHOU KONG5 and XINRI ZHANG 1 1State Key Laboratory for Pneumoconiosis of National Health Commission, Key Laboratory of Prevention, Treatment and Fundamental Studies for Respiratory Diseases of Shanxi, Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University; 2Department of Ultrasonic Imaging, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001; 3School of Medical Application Technology, Shenyang Medical College, Shenyang, Liaoning 110034; 4Department of Clinical Laboratory, People's Hospital of Lüliang, Lüliang, Shanxi 033000; 5Key Laboratory of Cellular Physiology of The Ministry of Education and Department of Pathology, Shanxi Medical University, Yingze, Taiyuan, Shanxi 030001, P.R. China Received July 13, 2022; Accepted February 22, 2023 DOI: 10.3892/ijo.2023.5505 Abstract. Lung cancer is the leading cause of cancer‑related mortality worldwide. Non‑small cell lung cancer (NSCLC) is the most common pathological subtype of lung cancer and is associated with low 5‑year overall survival rates. Therefore, novel and effective chemotherapeutic drugs are urgently required for improving the survival outcomes of patients with lung cancer. Cyclovirobuxine D (CVB‑D) is a natural steroidal alkaloid, used for the treatment of cardiovascular diseases in Traditional Chinese Medicine. Several studies have also demonstrated the antitumor effects of CVB‑D. Therefore, in the present study, the therapeutic effects of CVB‑D in lung cancer and the underlying mechanisms were investigated using the in vivo xenograft model of NSCLCin nude mice and in vitro experiments with the NSCLC cell Correspondence to: Dr Pengzhou Kong, Key Laboratory of Cellular Physiology of The Ministry of Education and Department of Pathology, Shanxi Medical University, 56 South Xinjian Road, Yingze, Taiyuan, Shanxi 030001, P.R. China E‑[mail: kongpengzhou@sxmu.edu.cn](mail: kongpengzhou@sxmu.edu.cn) Dr Xinri Zhang, State Key Laboratory for Pneumoconiosis of National Health Commission, Key Laboratory of Prevention, Treatment and Fundamental Studies for Respiratory Diseases of Shanxi, Department of Respiratory and Critical Care Medicine, First Hospital of Shanxi Medical University, 85 South Jiefang Road, Yingze, Taiyuan, Shanxi 030001, P.R. China E‑mail: [ykdzxr61@163.com](ykdzxr61@163.com) Key words: cyclovirobuxine D, RNA‑sequencing, non‑small cell lung cancer, KIF11‑CDC25C‑CDK1‑CyclinB1 signaling pathway, ultrasonic imaging lines. Bioinformatics analyses of RNA‑sequencing data, and cell‑based functional assays demonstrated that CVB‑D treat‑ ment significantly inhibited in vitro and in vivo NSCLC cell proliferation, survival, invasion, migration, angiogenesis, epithelial‑to‑mesenchymal transition and G2/M phase cell cycle. CVB‑D exerted its antitumor effects by inhibiting the KIF11‑CDK1‑CDC25C‑cyclinB1 G2/M phase transition regulatory oncogenic network and the NF‑κB/JNK signaling pathway. CVB‑D treatment significantly reduced the sizesand weights and malignancy of xenograft NSCLC tumors in the nude mice. In conclusion, the present study demonstrated that CVB‑D inhibited the growth and progression of NSCLC cells by inhibiting the KIF11‑CDK1‑CDC25C‑CyclinB1 G2/M phase transition regulatory network and the NF‑κB/JNK signaling pathway. Therefore, CVB‑D is a promising drug for the treatment of NSCLC patients. Introduction Lung cancer is the leading cause of cancer incidence, morbidity and mortality worldwide (1) . Non‑small cell lung cancer (NSCLC) is the most common subtype of lung cancer that accounts for ~80% of lung cancer cases and is associated with low 5‑year overall survival (OS) (

FAQs

What problem does the study address in non-small cell lung cancer?

Non-small cell lung cancer has low 5-year overall survival, especially in advanced or metastatic cases where chemotherapy resistance leads to poor outcomes. The study aims to find more effective chemotherapeutic options.

What is Cyclovirobuxine D (CVB-D) and why was it investigated?

CVB-D is a natural steroidal alkaloid used for cardiovascular diseases in Traditional Chinese Medicine. Prior studies suggested antitumor effects, prompting investigation of its role in lung cancer.

How does CVB-D exert antitumor effects according to the study?

CVB-D significantly inhibits NSCLC cell proliferation, survival, invasion, migration, angiogenesis, EMT, and G2/M phase progression. The mechanisms involve suppression of the KIF11-CDC25C-CDK1-CyclinB1 G2/M phase transition regulatory network and the NFκB/JNK signaling pathway.

Sep 24, 2026

Uploaded by Noah