ABSTRACT
PURPOSE: Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most common estrogen-related functional pituitary tumors. As an agonist of the dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma progression. On the other hand, it is not always effective in clinical application. Although a dopamine D2 receptor deficiency contributes to the impaired efficiency of bromocriptine therapy to some extent, it is unknown whether there some other underlying mechanisms leading to bromocriptine resistance in prolactinoma treatment. That is the main point addressed in this project. MATERIALS AND METHODS: Human prolactinoma samples were used to analyze the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin-3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction partners of SKP2 were also detected after a bromocriptine treatment in 293T. Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells. RESULTS: Compared to normal pituitary samples, most prolactinoma samples exhibit higher levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2 and resulted in SKP2 overexpression to a greater extent, which in turn compromised its pro-apoptotic effect. As a result, the bromocriptine treatment combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human prolactinoma cells. CONCLUSION: These findings indicated that SKP2 inhibition sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis. Moreover, a combined treatment of bromocriptine and C25 may contribute to the maximal apoptosis of human prolactinoma cells.
Subject(s)
Humans , Apoptosis , Bromocriptine , Half-Life , Hand , Pituitary Neoplasms , Prolactinoma , Receptors, Dopamine D2 , S-Phase Kinase-Associated ProteinsABSTRACT
Seeds of Trigonella foenum-graecum L., as a raditional Chinese medicine, are rich n steroidal saponins. The systematic research on steroidal saponins of Trigonella foenum-graecum, including the study on furostanol saponins and spirostanol saponins, the rapid characterization and dentification of steroidal saponins, and he analytical and preparative separation of C-25 R/S-spirostanol saponin diastereomers using supercritical fluid chromatography, was performed. The results of research are helpful to the development and utilization of Trigonella foenum-graecum seeds, and the methods could provide reference for the chemical research on other traditional Chinese medicines.
ABSTRACT
Objective To study the lymphoproliferative responses to HHV-6(Human Herpesvirus-6,HHV-6)among patients with oral squamous cell carcinoma,and to discuss the role of HHV-6 in the pathogenesis of oral squamous cell carcinoma.Methods IgG antibody to HHV-6 in plasma was identified by indirect immunofluorescence(IIF).Immuno-magnetic beads were used to prepare CD4+ T cells and CD8+ T cells.The proliferation of CD4+ T cells,CD8+ T cells and PBMCs stimulated with HHV-6 or anti-CD3 antibodies was measured by 3H-thymidine uptake.The percentage of CD4+ C25+ Treg cells(Regulatory T cell,Treg)within the peripheral blood CD4+ T cell compartment was analyzed by flow cytometry.Results Significantly higher proportion of patients with oral squamous cell carcinoma had IgG antibody to HHV-6(8/8) in plasma as compared with those in control subjects(12/20);The proliferative responses of PBMCs and CD4+ T cells from patients with oral squamous cell carcinoma to HHV-6 were significantly decreased as compared to those from HHV-6-infected and healthy individuals(P