PAFR/Stat3 axis maintains the symbiotic ecosystem between tumor and stroma to facilitate tumor malignancy

Stroma surrounding the tumor cells plays crucial roles for tumor progression. However, little is known about the factors that maintain the symbiosis between stroma and tumor cells. In this study, we found that the transcriptional regulator-signal transducer and activator of transcription 3 (Stat3) was frequently activated in cancer-associated fibroblasts (CAFs), which was a potent facilitator of tumor malignancy, and formed forward feedback loop with platelet-activating factor receptor (PAFR) both in CAFs and tumor cells. Importantly, PAFR/Stat3 axis connected intercellular signaling crosstalk between CAFs and cancer cells and drove mutual transcriptional programming of these two types of cells. Two central Stat3-related cytokine signaling molecules-interleukin 6 (IL-6) and IL-11 played the critical role in the process of PAFR/Stat3 axis-mediated communication between tumor and CAFs. Pharmacological inhibition of PAFR and Stat3 activities effectively reduced tumor progression using CAFs/tumor co-culture xenograft model. Our study reveals that PAFR/Stat3 axis enhances the interaction between tumor and its associated stroma and suggests that targeting this axis can be an effective therapeutic strategy against tumor malignancy.

Chrysin serves as a novel inhibitor of DGKα/FAK interaction to suppress the malignancy of esophageal squamous cell carcinoma (ESCC)

@#Among current novel druggable targets, protein–protein interactions (PPIs) are of considerable and growing interest. Diacylglycerol kinase α (DGKα) interacts with focal adhesion kinase (FAK) band 4.1-ezrin-radixin-moesin (FERM) domain to induce the phosphorylation of FAK Tyr397 site and promotes the malignant progression of esophageal squamous cell carcinoma (ESCC) cells. Chrysin is a multi-functional bioactive flavonoid, and possesses potential anticancer activity, whereas little is known about the anticancer activity and exact molecular mechanisms of chrysin in ESCC treatment. In this study, we found that chrysin significantly disrupted the DGKα/FAK signalosome to inhibit FAK-controlled signaling pathways and the malignant progression of ESCC cells both in vitro and in vivo, whereas produced no toxicity to the normal cells. Molecular validation specifically demonstrated that Asp435 site in the catalytic domain of DGKα contributed to chrysin-mediated inhibition of the assembly of DGKα/FAK complex. This study has illustrated DGKα/FAK complex as a target of chrysin for the first time, and provided a direction for the development of natural products-derived PPIs inhibitors in tumor treatment.

Effects ofSimiaosan on CTGF, BMP-7 Expression in Human Renal Tubular Epithelial Cell Induced by Uric Acid / 中国中医药信息杂志

Objective;To explore the mechanism ofSimiaosan drug-containing serum on prevention and treatment of renal fibrosis.Methods Human renal tubular epithelial cells (HK-2) were divided into blank group, model group, control group, and drug-containing serum high dosage group, medium dosage group and low dosage group. The expressions of CTGF and BMP-7 were determined by real-time PCR assay and immunocytochemistry.Results After the HK-2 cell was induced by uric acid (UA), the expression of CTGF significantly increased (P<0.05), the expression of BMP-7 significantly decreased (P<0.05). After intervened bySimiaosan, the expression of CTGF significantly decreased (P<0.05), the expression of BMP-7 significantly increased (P<0.05) and present dosage dependent.Conclusion Reducing the expression of CTGF and up-regulation the expression of BMP-7 and controlling epithelial-myofibroblast transdifferentiation may be the mechanism ofSimiaosan on prevention and treatment of renal fibrosis.

Correlation of Traditional Chinese Medical Syndrome Elements with Plasma Connective Tissue Growth Factor and Platelet-derived Growth Factor in Early Liver Cirrhosis Induced by Type B Hepatitis / 广州中医药大学学报

Objective To explore the correlation of traditional Chinese medical syndrome elements with plasma connective tissue growth factor ( CTGF) and platelet-derived growth factor ( PDGF) in early liver cirrhosis induced by type B hepatitis. Methods The distribution of traditional Chinese medical syndrome elements in early liver cirrhosis induced by type B hepatitis was analyzed, plasma contents of CTGF and PDGF were detected by enzyme-linked immunosorbent assay ( ELISA) , and the correlation of syndrome elements with CTGF and PDGF was discriminated. Results ( 1) The distribution of traditional Chinese medical syndrome elements in early liver cirrhosis induced by type B hepatitis showed as follows: the syndrome elements involved the viscera of liver and spleen, and the pathogenesis was characterized as dampness, heat, qi stagnation, and yin deficiency. ( 2) CTGF was closely related with spleen, gallbladder and dampness, with OR value being 1.598, 1.567, 2.797, respectively. PDGF was closely related with heat, with OR value being 1.134. Conclusion Early liver cirrhosis induced by type B hepatitis mainly affects the viscera of liver and spleen, the pathogenesis is characterized by dampness, heat, qi stagnation, and yin deficiency. The patients with higher CTGF are apt to show the pathological changes of spleen, gallbladder, dampness, and have the syndrome el-ements of spleen, gallbladder, dampness. The patients with higher PDGF are apt to show the pathological changes of heat, and have the syndrome element of heat.

Clinic research of treating perimenopausal syndrome tongue demonstration changes by Chaihu Shugan Decoction / 中华中医药杂志

Objective: To explore the tongue epithelial cell apoptosis quantitatively to analysis tongue demonstration change mechanism of perimenopausal syndrome by Chaihu Shugan Decoction. Methods: Patients with perimenopausal syndrome 60 cases, divided into kidney yin deficiency (30 cases), deficiency of both kidney yin and yang (30 cases), 30 healthy cases in normal group. The treatment course lasted for 2 months. The flow cytometry was used to detect the tongue epithelial cell apoptosis. Results: The tongue epithelial cell apoptosis rate of perimenopausal syndrome patients was higher than that in the normal group (P