Marsdenia tenacissima (Roxb.) Moon injection exerts a potential anti-tumor effect in prostate cancer through inhibiting ErbB2-GSK3ß-HIF1α signaling axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima injection (MTE), a traditional Chinese medical injection extracted from the rattan of Marsdenia tenacissima (Roxb.) Moon, has been approved for clinical use in China as an adjuvant therapeutic agent in multiple cancers, including esophageal cancer, gastric cancer, lung cancer, and liver cancer. However, the activity and mechanism of MTE on prostate cancer (PCa) remain to be defined. AIM OF THE STUDY: To investigate the activity and the underlying mechanism of MTE in the treatment of PCa. MATERIALS AND METHODS: The component characterization of MTE was analyzed by HPLC-CAD-QTOF-MS/MS technology. Cell Counting Kit-8 (CCK-8) assay was used to assess PCa cell proliferation. Colony formation assay was applied to detect the clonogenic ability of the cells. MetaboAnalyst5.0 database was employed to analyze the altered metabolites of PC3 cells treated with MTE obtained by UPLC-QTOF-MS/MS. Combined with metabolomics analysis and network pharmacology, we predicted the potential targets, which further were verified by Western Blot, RT-qPCR, and Immunohistochemistry assays. Finally, SeeSAR software was applied to predict the potential active components of MTE against PCa. RESULTS: A total of 21 components in MTE were confirmed by HPLC-CAD-QTOF-MS/MS analysis. MTE inhibited the proliferation and colony formation of PCa cells. A total of 20 metabolites closely related to glycerophospholipid metabolism, glycolysis/gluconeogenesis, and tricarboxylic acid (TCA) cycle were significantly changed in PC3 cells treated with MTE. The network pharmacology analysis revealed that MTE suppressed the growth of PC3 cells might by regulating the ErbB2-GSK3ß-HIF1α signaling axis. Furthermore, we also confirmed that stimulation of MTE significantly inhibited the phosphorylation of ErbB2 at Tyr877 and the activities of its downstream signal transducers (GSK3ß and HIF1α) in PCa, as well as the mRNA levels of critical factors (IDH2, LDHA, and HIF1A) in the tricarboxylic acid (TCA) cycle. Molecular docking further suggested that Tenacissimoside E, cryptochlorogenic acid, and scopoletin might be the active ingredients of MTE for PCa treatment. CONCLUSION: This study proposed that MTE exerts a potential anti-tumor effect in PCa through inhibiting ErbB2-GSK3ß-HIF1α signaling axis, which may be related to the TCA cycle.

Total Flavonoids of Litchi Seed Attenuate Prostate Cancer Progression Via Inhibiting AKT/mTOR and NF-kB Signaling Pathways.

Litchi seeds have been traditionally used in Chinese herbal formula for urologic neoplasms including prostate cancer (PCa). However, the effective components of Litchi seeds and the mechanisms of their actions on PCa cell growth and metastasis remain unclear. In this study, we investigated the effects and molecular mechanisms of the Total Flavonoid of Litchi Seed (TFLS) in PCa PC3 and DU145 cell lines. We found that TFLS significantly inhibited the PCa cell proliferation, induced apoptosis, and prevented cell migration and invasion. Furthermore, we observed that TFLS upregulated the expression of epithelial biomarker E-cadherin and downregulated mesenchymal biomarker Vimentin. TFLS also increased the expression of cleaved-PRAP and Bax, and decreased the expression of Bcl-2 in both PC3 and DU145 cells. Besides, TFLS inhibited AKT signaling pathway by reducing the phosphorylation of AKT and activities of downstream signal transducers including mTOR, IκBα and NF-kB. Finally, TFLS treated mice exhibited a significant decrease in tumor size without toxicity in major organs in vivo. These results indicated that TFLS could suppress PCa cell growth in vivo and inhibit PCa cell proliferation and metastasis in vitro through induction of apoptosis and phenotypic reversal of EMT, which may be achieved by inhibiting the AKT/mTOR and NF-κB signaling pathways. Taken together, our data provide new insights into the role of TFLS as a novel potent anti-cancer agent for the treatment of PCa.

[Research progress of double-bundle anterior cruciate ligament reconstruction in adolescents].

OBJECTIVE: To review the advances in double-bundle anterior cruciate ligament (ACL) reconstruction in adolescents at home and abroad. METHODS: Recent literature about double-bundle ACL reconstruction in adolescents at home and abroad was extensively consulted, and the relationship between bone canal and epiphyseal plate, clinical verification of surgical safety, and clinical effectiveness of double-bundle ACL reconstruction in adolescents were summarized and analyzed. RESULTS: Double-bundle ACL reconstruction has certain advantages in clinical stability and re-rupture rate when compared with single-bundle ACL reconstruction in adolescents, and there is no significant difference in safety between them. CONCLUSION: Double-bundle ACL reconstruction in adolescents can achieve lower re-rupture rate and better stability when compared with single-bundle reconstruction. However, the sample size of clinical research is too small, and the follow-up time is too short, so the effectiveness needs to be continuously observed.

[Effect of L-tyrosine on 3beta-HSD activity of rat luteal cells in vitro].

AIM: To study the effects of L-tyrosine on 3beta-HSD activity of rat luteal cells in vitro. METHODS: Luteal cells were isolated from ovary tissues of female rats pretreated with PMSG and hCG. Luteal cells were cultured with 95% oxygen and 5% carbon dioxide in 37 degrees C. 3beta-HSD activity was measured by radioimmunoassay (RIA). RESULTS: (1) 0.2 mmol x L(-1) and 2.0 mmol x L(-1) L-tyrosine significantly inhibited 3beta-HSD activity. (2) 0.2 mmol x L(-1) L-tyrosine exerted different effects on 3beta-HSD activity at different concentrations of pregnenolone (Ph). It increased 3beta-HSD activity at 0.1 micromol x L(-1) and 1 micromol x L(-1) of Pn concentration. With further increase in the concentration of Pn to 100 micromol x L(-1), the stimulating effect of L-tyrosine was switched to suppression effect. (3) L-tyrosine and L-tyrosine hydrazide both inhibited 3beta-HSD activity induced by hCG. CONCLUSION: L-tyrosine affects 3beta-HSD activity of rat luteal cells in vitro. L-tyrosine and tyrosine hydrazide inhibits hCG induced 3beta-HSD activity.