Журнал гепатологии и желудочно-кишечных расстройств
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Progesterone and selective ligands of membrane progesterone receptors increase apoptosis in human pancreatic adenocarcinoma cells BxPC3 via p38 MAPK activation.

A.I. Goncharov, I.S. Levina, I.A. Morozov, P.M. Rubtsov, O.V. Smirnova, T.A. Shchelkunova

                                                                                                                                                                                                       

 

Progesterone (P4) regulates the women reproductive functions by acting primarily through nuclear receptors (nPRs). However, its functions are not limited to the reproductive sphere. In 2003 membrane progesterone receptors (mPRs) were identified. We recently discovered selective ligands of these receptors: 19-hydroxypregn-4-en-20-one (I) and 19- hydroxy-5β-pregn-3-en-20-one (II) that do not interact with nPRs. Maximal level of mPRs expression was found in BxPC3 human pancreatic adenocarcinoma cells lacking of nPRs.

 

Aim of Research: The aim of this work was to evaluate the effects of P4 and mPRs selective ligands (I) and (II) on apoptosis of BxPC3 cells and to identify the mediators of their action.

 

Method: Activation of p38 MAPK and JNK by different concentrations of steroids was analyzed by Western blotting with antibodies against phosphorylated forms of these protein kinases. The levels of DNA fragmentation in BxPC3 cells in the absence or presence of p38 MAPK and JNK inhibitors were measured by TUNEL assay with following flow cytometry analysis.

Data were analyzed using GrapgPad Prism 6 software. For the comparative analysis ordinary one-way ANOVA Kruskal-Wallis test was performed. Statistical significance was considered for a p value < 0, 05.