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OBJECTIVE@#Aconite is a traditional Chinese herbal medicine that has been found to inhibit the development of liver cancer; however, its exact molecular mechanisms in this process remain unclear. This study explores how aconite aqueous extract (AAE) inhibits hepatocellular carcinoma (HCC).@*METHODS@#An in vivo mouse model of subcutaneous liver cancer was established. After AAE treatment, immunohistochemistry (IHC) was used to determine the effect of AAE on natural killer (NK) cells. Subsequently, C57BL/6 mice were used to establish the subcutaneous tumor model, and a group of these mice were treated with anti-PK163 antibody to remove NK cells, which was verified by flow cytometry and IHC. The effect of AAE on the proliferation of HCC cells in vitro was determined using cell counting kit-8. The effect of AAE on chemokine production in HCC cells was measured using real-time quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The effect of AAE on the migration of NK cells was determined using a transwell assay. Finally, the molecular mechanism was investigated using the Western blotting method.@*RESULTS@#We demonstrated that the ability of AAE to induce overexpression of the cytokine C-C motif chemokine ligand 2 (CCL2) in HCC cells is fundamental to the infiltration of NK cells into the tumor bed. Mechanistically, we found that the upregulation of CCL2 was achieved by the activation of c-Jun N-terminal kinase but not extracellular regulated protein kinase or p38.@*CONCLUSION@#Our findings suggest that AAE can be used as an effective immune adjuvant to enhance antitumor immunity by increasing NK cell infiltration into tumors, which could help to improve the efficacy of HCC treatments. Please cite this article as: Yang KD, Zhang X, Shao MC, Wang LN. Aconite aqueous extract inhibits the growth of hepatocellular carcinoma through CCL2-dependent enhancement of natural killer cell infiltration. J Integr Med. 2023; 21(6): 575-583.
Subject(s)
Animals , Mice , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Aconitum , Ligands , Mice, Inbred C57BL , Killer Cells, Natural/metabolism , Chemokines/pharmacology , Cell Line, TumorABSTRACT
Objective To analyze the infiltration abundance of macrophage M2 in breast cancer tissues and explore the correlation between VSIG4 and macrophage M2 and the potential mechanism of regulating the invasion and migration of breast cancer patients. Methods We downloaded the RNA-seq data of TCGA-BRCA and assessed the infiltration abundance of immune cells in the samples by CIBERSORT, and established a prognostic risk prediction model. Then, we analyzed the effect of macrophage M2 and VSIG4 on the prognosis of breast cancer patients. In addition, we analyzed the signaling pathway associated with VSIG4 by gene set enrichment analysis and predicted its upstream regulation of miRNA. Results The infiltration abundance of macrophage M2, age, PR status and pathological stage were involved in the establishment of risk prediction model, and the model had a good prediction performance (AUC=0.816). High infiltration of macrophage M2 (HR=1.35, P < 0.05) and high expression of VSIG4 (HR=1.4, P=0.039) suggested poor prognosis of breast cancer patients. VSIG4 could be regulated by upstream miR-29a-3p and significantly correlated with Toll-like receptor, cell adhesion, production and release of cytokine. Conclusion VSIG4 is significantly associated with breast cancer patients' prognosis and infiltration of macrophage M2, regulated by the upstream miR-29a-3p and promotes the invasion and migration of breast cancer cells. It can be used as a potential prognostic marker for breast cancer.
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The only possible cure for patients with locally advanced colorectal cancer is multivisceral resection. With the development of oncological surgery techniques and various types of targeted cancer therapy drugs, treatment modality of multidisciplinary team has been proposed and implemented. How to choose the optimal treatment strategy is a common problem.
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Objective To investigate the role of pituitary tumor transforming gene 1 (PTTG1) in the growth and invasion of human glioma cell line by introduction of exogenous microRNA to silence PTTG 1 gene expression. Methods Two double-stranded DNA pcDNA6.2-GW/EmGFP-miR vectors (MIR-1, MIR-2) targeting human PTTG1 mRNA and a negative control plasmid (Neg) were constructed, and were transfected into human U251 cells with high metastatic potentials. Real-time PCR and Western blotting were used to quantify the mRNA and protein levels of PTTG1, respectively. Proliferation and invasiveness of transfected U251 cells were analyzed by MTT assay and Matrigel invasion assay. Results After transfection, Expression of PTTG1 mR.NA was inbibited significantly with inhibitory rates of 87.6% in MIR-2 group, and the protein levels were significantly lower than those of the other groups. There was significant difference in cellular growth rate among the 3 groups. The growth inhibiting rates in the MIR-2 group are 10.7%-34.7%. The migrating number of U251 cells transfected with MIR-2 with relative percentage (12.3±1.0)% was also significantly decreased as compared the Neg group (24.7±1.4)% and Mock group (24.0±2.0)%. Conclusion Introduction of exogenous miRNA to U251 cell line by transfection of MIR-2 can effectively reduce the PTTG1 expression, which can significantly inhibit the proliferation and decrease the invasiveness of glioma cells.
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Objective To investigate the expression of anchor attachment protein(AAP)in colorectal carcinoma tissues and serum level of AAP in colorectal carcinoma patients and to identify the relationship among AAP expression,lymph node and liver metastases.Methods Immunohistochemistry was used to detect AAP expression,and ELISA was used to test AAP level in peripheral vein blood in 83 patients with colorectal carcinoma.Results The expression rate in normal colorectal mucosa,primary cancer,lymph nodes and liver metastases were 20.5%、53.0%、69.8% and 80.0%,respectively.The positive rate of AAP in primary cancer,lymph nodes and in liver metastasesfoci was higher than that in normal mucosa(P