Prangos ferulacea is a widely recognized and valuable medicinal herb known for its diverse biological characteristics. Our study was conducted to evaluate the anticancer and immunomodulatory effects of P. ferulacea. Ethyl acetate, methanol, and aqueous extracts were prepared from P. ferulacea, and the MTT assay was used to measure antiproliferation activity against 5 cancer cell lines (MDA-MB231, T47-D, HeLa, EMT6/P, and Vero). The 3 extracts underwent a qualitative LC/MS spectrometry analysis to determine each extract's composition. The MTT test was used to measure the proliferation of lymphocytes. Extracts were evaluated for their effects on macrophages phagocytic activity and pinocytosis function using the nitro blue tetrazolium assay and the neutral red method, respectively. The impact of ethyl acetate and methanol was assessed in mice inoculated with EMT6/P using the in vivo model, and the tumor size was measured. Results showed that ethyl acetate and methanol extracts had the highest activity against T47-D with IC50 values of 0.019 mg/ml. The ethyl acetate extract exhibited moderate effectiveness against the following cell lines: MDA-MB-231 and EMT6/P with IC50 values of 0.104 and 0.255 mg/ml, respectively. Meanwhile, methanol extract showed activity against MDA-MB231 and EMT6/P cell lines and had IC50 values of 0.214 and 0.31 mg/ml, respectively. Regarding immunomodulatory assays, the methanol extract, followed by the ethyl acetate extract, significantly increases lymphocyte proliferation and macrophage phagocytosis activity. Aqueous extracts increase the activity of pinocytosis. Both ethyl acetate and methanol extracts reduced tumor size by 61.46% and 34.47%, respectively. They also decreased the average weight of the tumor cells in the in vivo model. The results of P. ferulacea have valuable activity against cancer cells and stimulate the immune system. However, further molecular investigations are required to understand the mechanism of action of P. ferulacea activity.

This study delves into the therapeutic effects of combining GEM and Angelica polysaccharide (APS) on triple-negative breast cancer. In vitro, proliferation, apoptosis of 4T-1 cells and MDSC were detected by flow cytometry. Migration of 4T-1 cell was detected by scratch healing experiment after treatment by GEM (0, 2.5, 5 μM), APS (160,320 mg/ml), or GEM + APS (2.5 μM + 160 mg/ml, 5 μM + 320 mg/ml). In vivo, 4T-1 cells were injected into the mammary fat pad under the mammary gland of BALB/c mice to establish an orthotopic breast cancer tumor model. They were randomly divided into control group (0.9% normal saline + ultrapure water), GEM group (0.9% normal saline preparation, 100 mg/kg, intraperitoneal injection twice a week), APS group (ultrapure water preparation, 200 mg/kg, intraperitoneal injection once a day), GEM + APS group (GEM 100 mg/kg, intraperitoneal injection twice a week and APS 200 mg/kg, intraperitoneal injection once a day) for 3 weeks. The proportion of immune cells in the spleen and tumor microenvironment were detected by flow cytometry, immunofluorescence and Mindray hematology analyzer. The tumor volume and weight, spleen index were recorded. The in vitro experimental results revealed that GEM effectively inhibited the proliferation and migration of 4T-1 cells and induced apoptosis in both 4T-1 cells and MDSCs. In contrast, APS had no impact on 4T-1 cells or MDSCs. The in vivo experimental findings indicated that compared with the single-drug treatment groups, the combination treatment of GEM + APS more effectively regulated the proportion of peripheral and local anti-tumor MDSCs and T cells, and more significantly curbed the progression of breast cancer in mice. APS can exert a synergistic effect through immune regulation to enhance the therapeutic efficacy of GEM on triple-negative breast cancer. It aims to offer novel insights for the clinical application of combining GEM with immunotherapy for patients with triple negative breast cancer.

Background:Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem with no widely applicable solutions. Modified Wen Luo Tong (mWLT) was designed specifically for paclitaxel-related CIPN, yet its efficacy and mechanisms remain unclear. This study aimed to investigate its therapeutic effects and potential mechanisms via network pharmacology and animal experimental validation.Methods:Paclitaxel-induced CIPN rat models were treated with mWLT pediluvium. The effect of mWLT was estimated by behavior test. The components and targets of 5 herbs in mWLT were screened from TCMSP and TCMIP databases. CIPN-related targets were retrieved from Genecards and DisGeNET. Networks of gene ontology and pathway associations related to intersection targets were constructed and visualized. A pharmacological network encompassing the intersecting genes and active components was mapped out. A protein-protein interaction network was established for these intersecting targets and visualized using Cytoscape software. Finally, the findings derived from network pharmacology were validated through a series of in vivo experiments, including ELISA, Western Blot, immunohistochemistry and RT-qPCR. Molecular docking was used to predict binding sites between small molecules of mWLT and CX3CR1.Results:mWLT ameliorates mechanical withdrawal threshold of CIPN model rats. Three hundred and three targets of mWLT against CIPN were identified through intersection analysis, and 8 hub targets such as IL6, TNF and STAT3 were pinpointed. Enrichment analysis of intersection targets highlighted cellular response to cytokine stimulus, JAK-STAT3 pathway and NF-κB pathway. Thus, we speculated that mWLT may exert its effects by acting on IL6 and TNF, subsequently regulating IL6-JAK-STAT3 and TNFα-NF-κB signaling pathway, ultimately mitigating CIPN. Experimental validation demonstrated that mWLT significantly decreased the levels of IL-6, IL-1β and TNF-α in both spinal cord and plasma. Additionally, mWLT downregulated the phosphorylation of JAK, STAT3 and NF-κB in spinal cord. Further analyses using Immunohistochemistry, Western Blot and ELISA confirmed that mWLT reduced the protein expression of CX3CL1. RT-qPCR results revealed downregulation of Cx3cl1 and Cx3cr1 mRNA level in spinal cord and dorsal root ganglia. Molecular docking predicts 4 potential of compounds derived from mWLT to treat CIPN targeting CX3CR1.Conclusion:mWLT exerts therapeutic effects in the treatment of CIPN by inhibiting CX3CL1/CX3CR1 axis and modulating JAK-STAT3 and NF-κB pathway.

Background:Oral squamous cell carcinoma (OSCC) is an invasive cancer with a high rate of metastasis and recurrence. Anthraquinone natural active element sennoside A (SA) has demonstrated a repressive effect on several malignancies. Its impact on OSCC is still unknown, though.Methods:The toxicity effect of SA on OSCC cells was examined by CCK8, to screen the appropriate concentrations for following assays. The effect of SA on proliferation, ferroptosis and immune evasion of OSCC was assessed by CCK-8, DCHF-DA staining, biochemical detection, ELISA, and western blotting. The mechanism of SA on OSCC was determined by western blotting and immunofluorescence. Besides, in vivo effect of SA was investigated on tumor-bearing mice using HE staining, immunohistochemistry, and western blotting.Results:SA reduced SCC7 and CAL27 cell viability, with a IC50 values of 94.38 and 77.41 μM, respectively. SA downregulated the expressions of GPX4 and xCT expression and the SOD level, but elevated the levels of ROS, MDA, and Fe2+ in SCC7 and CAL27 cells. SA decreased the PD-L1 expression, whereas increased the cytotoxicity of CD8+ T cells and the concentrations of IFN-γ, IL-2, and TNF-α of SCC7 and CAL27 cells. Mechanically, SA reduced the phosphorylation of NF-κB and IκBα in SCC7 and CAL27 cells. Also, RANKL treatment reversed the outcomes of indicators involved in proliferation, ferroptosis and immune evasion in SCC7 cells. In vivo, SA reduced tumor weight and size, the expression levels of GPX4 and PD-L1 and the phosphorylation of NF-κB and IκBα, but enhanced the IFN-γ level in mice xenografted with SCC7 cells.Conclusion:SA suppressed proliferation and immune evasion, but induced ferroptosis through the inactivation of NF-κB pathway in OSCC.

Context:Hepatocellular carcinoma (HCC) is a malignant tumor with high global incidence and mortality rates. Jianpi Huayu Formula (JPHY) has demonstrated therapeutic potential in HCC, but its underlying mechanisms remain unclear.Objective:This study aimed to investigate the anti-HCC effects of JPHY and its molecular mechanisms, focusing on its regulatory roles in vasculogenic mimicry (VM) formation and epithelial-mesenchymal transition (EMT) progression.Methods:Sk-Hep-1 cells were treated with 5%, 10%, or 20% JPHY-medicated serum (JPHY-MS). Cell proliferation, migration, VM, and EMT were assessed using CCK-8, wound healing, tube formation, and Western blot assays. Molecular docking was employed to analyze the binding between core components of JPHY and CXCR4. A stable CXCR4-overexpressing cell line was established, and the regulatory effect of CXCR4 on the Smad2/3 pathway was observed following intervention with the Smad2/3-specific inhibitor SB431542. Finally, a retrospective study was conducted using JPHY-MS intervention. In vivo experiments: Mice bearing HCCLM3 xenografts were divided into control, model, low-dose (6.24 g/kg), and high-dose (24.96 g/kg) JPHY groups. Tumor size and body weight were measured every 3 days. The effects of drug intervention on the CXCR4-Smad2/3 pathway, EMT, and VM were examined via immunohistochemistry (IHC), CD31/PAS double staining, and Western blot analysis.Results:JPHY may impede HCC progression and metastasis through CXCR4 downregulation-mediated suppression of Smad2/3 signaling pathway activation, concomitantly modulating VM formation and EMT processes.Conclusion:JPHY suppresses HCC progression by targeting the CXCR4-Smad2/3 pathway, highlighting its potential as a novel HCC therapeutic.

Limitations in the therapies of triple-negative breast cancer, the strongest invasive subtype of breast cancer, have led to unsatisfactory clinical outcomes for patients. The efficacy of immunotherapy, an emerging treatment choice for triple-negative breast cancer, is highly related to the functional expression of each immune cell in the tumor immune microenvironment. Therefore, improving the immune response of immune cells in the tumor immune microenvironment is beneficial to enhance the effects of immunotherapy for triple-negative breast cancer clinically. There is now growing evidence that the active ingredients in traditional Chinese medicine, especially herbal medicine can influence the correlation of 2 major immune cell subpopulations in the tumor microenvironment of triple-negative breast cancer: tumor-infiltrating lymphocytes (T lymphocytes, B lymphocytes, Natural killer cells) and tumor-associated myeloid cells (macrophages, myeloid-derived suppressor cells, dendritic cells, neutrophils) expression of immune effect. This suggests that traditional Chinese medicine can effectively improve the immunosuppressive state of tumor microenvironment and enhance the effects of clinical immunotherapy for triple-negative breast cancer.