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. This 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 9 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, this 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.

Ampelopsin Inhibits Cell Viability and Metastasis in Renal Cell Carcinoma by Negatively Regulating the PI3K/AKT Signaling Pathway

“…Curcumin inhibited cell proliferation and motility by suppression of TROP2 in bladder cancer [ 18 ]. In addition, the traditional Chinese medicine Bu-Shen-Jian-Pi-Fang has been reported to attenuate the glycolysis and immune escape of clear cell RCC [ 19 ]. Nevertheless, effective drugs are still needed to improve the prognosis of RCC patients.…”

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“…Advanced renal cancer is mainly treated by surgical resection of tumor lesions combined with biological therapy, endocrine therapy, and immunotherapy, which is not effective and patients are prone to intolerance [ 3 ]. Based on the holistic view and syndrome differentiation, traditional Chinese medicine believes that renal cell cancer is caused by deficiency of kidney qi and aggregation of pathogenic toxins [ 4 ]. The application of TCM treatment can improve the healthy qi, stabilize the cancer focus, prevent recurrence and metastasis, and thus achieve the purpose of improving the quality of life of patients and prolonging their survival [ 5 , 6 ].…”

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