Experimental Oncology, 2011, № 3

Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study

Sat, 01 Jan 2011 00:00:00 GMT

Human beta-defensin-2 controlS cell cycle in malignant epithelial cells: in vitro study Zhuravel, E.; Shestakova, T.; Efanova, O.; Yusefovich, Yu.; Kytvin, D.; Soldatkina, M.; Pogrebnoy, P. Aim: In the present research we analyze the mechanism of human beta-defensin-2 (hBD-2) influence on cultured malignant epithelial cell growth. Materials and Methods: The analysis of a concentration-dependent effect of recombinant hBD-2 (rec-hBD-2) on cell growth patterns and cell cycle distribution has been performed in vitro with 2 cell lines (human lung adenocarcinoma A549 cells and human epidermoid carcinoma A431 cells) using MTT test, flow cytometry and direct cell counting. To study intracellular localization of hBD-2 immunocytofluorescent and immunocytochemical analyses were applied, and effect of hBD-2 on signal cascades involved in cell cycle regulation has been studied by Western blotting. Results: According to our data, rec-hBD-2 exerts a concentration-dependent effect on the viability of cultured A549 and A431 cells. It causes proproliferative effect at concentrations below 1 nM, significant suppression of cell proliferation at concentration range from 10 nM to 1 µM (p<0.05), and cell death at higher concentrations. Using flow cytometry we have demonstrated that hBD-2 dependent growth suppression is realized via cell cycle arrest at G1/S phase (p<0.05). Also, we have registered significant activation of pRB and decreased expression of Cyclin D1 in cells treated with the defensin compared to untreated control cells, while the expression of p53 remains unaffected. The study of intracellular localization of hBD-2 in these cells has revealed that exogeneously added defensin molecules enter the cells, are distributed throughout the cytoplasm and could be detected in cell nuclei. The model study using A549 cells treated with 1,25-(OH)2D3 has shown similar cell growth suppression effect of native endogenously produced hBD-2. Conclusion: The results of our study suggest that in malignant epithelial cells hBD-2 may control cell growth via arrest of G1/S transition and activation of pRB.

Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice

Sat, 01 Jan 2011 00:00:00 GMT

Effect of vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and lewis lung carcinoma metastasis in mice Amikishieva, A.V.; Ilnitskaya, S.I.; Nikolin, V.P.; Popova, N.A. Aim: To study the effect of new vasopressin V1b receptor antagonist, SSR149415, on anxiety-like behavior and Lewis lung carcinoma metastasis in the anxious adult male mice of C57Bl/6J strain. This type of receptors was thought to act as potential targets mediating the effect of negative psychoemotional state on tumor progression. Methods: Anxiety-like psychoemotional state of the animals was produced using chronic social conflict model. Used behavioral tests were elevated plus-maze, social interaction test and open field test. Tumor cells were administrated on background of double or sixfold SSR149415 injections and the number of metastases in the lung were calculated 17 days later. Results: SSR149415 reduced the anxiety-like behavior measured in the elevated plus-maze and social interaction tests and did not affect locomotor activity in the open field test. Double and sixfold administration of the compound to such mice before and after inoculation of the tumor cells produced no effect on the metastasis rate. Conclusion: vasopressin V1b receptor is involved in the mediation of anxious behavior of animals but is not involved in the mechanism underlying the influence of negative psychoemotional state on Lewis lung carcinoma metastasis.

The role of interferon as a modifier of epithelial-mesenchymal transition in tumor cells

Sat, 01 Jan 2011 00:00:00 GMT

The role of interferon as a modifier of epithelial-mesenchymal transition in tumor cells Kudryavets, Yu.I.; Bezdenezhnykh, N.O.; Lykhova, O.O.; Semesiuk, N.I.; Vorontsova, A.L.

Drug resistance associated properties of blasts subpopulations with different CD34 expression in childhood acute lymphoblastic leukemia (ALL)

Sat, 01 Jan 2011 00:00:00 GMT

Drug resistance associated properties of blasts subpopulations with different CD34 expression in childhood acute lymphoblastic leukemia (ALL) Shman, T.V.; Fedasenka, U.U.; Savitski, V.P.; Kustanovich, A.M.; Aleinikova, O.V. Aim: The objective of this study was to investigate expression of drug resistance associated genes in CD34+ and CD34- leukemic subpopulations in childhood acute lymphoblastic leukemia (ALL). Methods: ALL samples with heterogeneous CD34 expression were separated into CD34-positive and CD34-negative subpopulations and mRNA levels of MDR1, LRP , BCRP and BCL-2 genes were compared. Results: BCL-2 gene expression levels did not differ significantly between CD34+ vs CD34− subpopulations in most analyzed ALL cases. Oppositely, MDR1 gene had >two-fold differences in expression levels between subpopulations in the majority of ALL cases. In T-lineage ALL CD34− fractions had increased level of BCRP and LRP genes in comparison with CD34+ ones whereas in most of B-lineage ALL expression of these genes did not differ. Conclusion: It was not found the unique pattern of resistance related genes expression in CD34+ vs CD34− subpopulations. However, in majority of studied pediatric ALL cases with CD34 heterogeneous expression one of subpopulations (positive or negative) could have an advantage for survival through elevated expression of drug resistance related genes.