Andrographolide suppresses triple-negative breast cancer proliferation through the p53/CDK1 axis: a multiscale analysis combining network pharmacology and machine learning.

Journal: Acta biochimica et biophysica Sinica
Published Date: Sep 25, 2026
(2)

Abstract

Triple-negative breast cancer (TNBC), a highly aggressive molecular subtype characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, remains a major clinical challenge, with a median overall survival of approximately 12-15 months in advanced-stage patients. Andrographolide (AG), a diterpenoid phytochemical derived from Andrographis paniculata, has demonstrated promising anti-inflammatory, antioxidant, and antitumor activities. However, its precise molecular and therapeutic mechanisms in TNBC remain poorly understood. AG inhibits the proliferation and metastasis of TNBC. Through an integrative approach combining network pharmacology and machine learning algorithms, including least absolute shrinkage and selection operator (LASSO) and random forest, cyclin-dependent kinase 1 (CDK1) has been identified as a critical molecular gene of AG. Experimental validation via western blot and immunofluorescence analyses reveal that AG treatment significantly downregulates CDK1 expression while concurrently upregulating the expression of the tumor suppressor p53, suggesting a functional interplay between these pathways. These mechanistic insights indicate that AG potentially exerts antiproliferative effects on TNBC cells through modulation of the p53/CDK1 signaling axis, thereby establishing a robust preclinical basis for its potential clinical translation in this challenging malignancy.

Authors

  • Xiaoyong Sun
    School of Information and Electronic Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, PR China.
  • Zhensheng Peng
    School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China.
  • Heng Luo
    Center for Computational Health, IBM T.J. Watson Research Center, 1101 Kitchawan Road, Yorktown Heights, NY, USA.
  • Xinping Li
    School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China.
  • Jinyi Wu
    School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China.
  • Junjie Peng
    Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • Xinhai Xiao
    School of Medical Information Engineering, Gannan Medical University, Ganzhou 341000, China.
  • Xuan Zheng
    AMOLF, Amsterdam, The Netherlands.
  • Hao Xiao
    State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; College of Physics and Information Science, Key Laboratory of Low-dimensional Quantum Structures, And Quantum Control of the Ministry of Education, Synergetic Innovation Center for Quantum Effects and Applications, Hunan Normal University, Changsha, China.
  • Haijian Zhong
    School of Medical and Information Engineering, Gannan Medical University, Ganzhou 341000, Jiangxi, China. Electronic address: [email protected].
  • Liang Zhang
  • Hua Wang
    Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Keywords

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