Traditional Chinese medicine Bu-Shen-Jian-Pi-Fang attenuates glycolysis and immune escape in clear cell renal cell carcinoma: results based on network pharmacology.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common malignant type of kidney cancer. The present study aims to explore the underlying mechanism and potential targets of the traditional Chinese medicine Bu-Shen-Jian-Pi-Fang (BSJPF) in the treatment of ccRCC based on network pharmacology. After obtaining the complete composition information for BSJPF from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, we analyzed its chemical composition and molecular targets and then established a pharmacological interaction network. Twenty-four significantly differentially expressed genes and nine pathways mainly related to tumor proliferation were identified and screened. Functional enrichment analysis indicated that the potential targets might be significantly involved in glycolysis and the HIF-1 signaling pathway. To further confirm the effect of BSJPF on ccRCC cell proliferation, a BALB/c xenograft mouse model was constructed. Potential targets involved in regulating glycolysis and the tumor immune microenvironment were evaluated using RT-qPCR. VEGF-A expression levels were markedly decreased, and heparin binding-EGF expression was increased in the BSJPF group. BSJPF also inhibited tumor proliferation by enhancing GLUT1- and LDHA-related glycolysis and the expression of the immune checkpoint molecules PD-L1 and CTLA-4, thereby altering the immune-rejection status of the tumor microenvironment. In summary, the present study demonstrated that the mechanism of BSJPF involves multiple targets and signaling pathways related to tumorigenesis and glycolysis metabolism in ccRCC. Our research provides a novel theoretical basis for the treatment of tumors with traditional Chinese medicine and new strategies for immunotherapy in ccRCC patients.

• Authors: Jinzhou Zheng, Wenhao Xu, Wangrui Liu, Haijia Tang, Jingen Lu, Kui Yu, Xiaoyun Song, Feng Li, Yu Wang, Rui Wang, Lili Chen, Hailiang Zhang, Yunhua Qiu, Gaomeng Wei, Xiqiu Zhou, Jianfeng Yang
• Journal: Bioscience reports (Biosci Rep) Vol. 41 Issue 6 (06 25 2021) ISSN: 1573-4935 [Electronic] England
• PMID: 34002799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Author(s).

Chemical References

• Antineoplastic Agents, Phytogenic
• Drugs, Chinese Herbal

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Carcinoma, Renal Cell (drug therapy, immunology, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Databases, Genetic
• Drugs, Chinese Herbal (pharmacology)
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Glycolysis (drug effects)
• Humans
• Kidney Neoplasms (drug therapy, immunology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Network Pharmacology
• Protein Interaction Maps
• Signal Transduction
• Tumor Burden (drug effects)
• Tumor Escape (drug effects)
• Tumor Microenvironment (immunology)
• Xenograft Model Antitumor Assays