RHAMM-selective peptides in a concentration of 10 μg/ml (2×10(-7) M) inhibited the growth of MDA-MB-231 breast cancer cells over 48 h. Treatment of cancer cells with RHAMM-selective peptides induced apoptosis and necrosis and increased caspase-3 activity (by 30%).
Introduction . The RHAMM (hyaluronan mediated mobility receptor) is overexpressed in many types of human cancer and increased synthesis of the RHAMM usually correlates with a poor prognostic factor. In this paper, we synthesized the peptide-RYQLHPYR modulating the activity of the RHAMM and examined the therapeutic potential of this RHAMM-targeting peptide as an antitumor agent.Objective . Study the effect of the synthetic peptide RYQLHPYR on viability, apoptosis, necrosis, caspase-3 / 7 activity, and invasion of prostate cancer cells.Materials and methods . The peptide RYQLHPYR was prepared by solid phase synthesis. Human prostate cancer cells (PC3 m-LN4), murine embryonic fibroblasts and murine embryonic fibroblasts (RHAMM- / -). To quantify the effect of the peptide on apoptosis and cell necrosis, ELISAPLUS was used. The activity of caspase-3 / 7 was determined by the colorimetric method. Evaluation of the anti-metastatic effect of the peptide in vitro was evaluated by invasion of cells by quantitative analysis of the area of degradation of fluorescent gelatin.Results . It was found that the peptide RYQLHPYR inhibited the growth of tumor cells PC3 m-LN4 at a concentration of 10 μg / ml (2 × 10–7 M) after 24 h by ~80 %. It was shown that the peptide stimulated the level of apoptosis in cancer cells, approximately 10-fold. It was found that the peptide increased the necrotic death of tumor cells by 2.5 times. During the research it was revealed that the peptide increased the caspase-3 / 7 activity in tumor cells by 2 times. At the same time, it was shown that RHAMM-targeting peptide had no significant effect on apoptosis and necrosis of normal cells (fibroblasts) and fibroblasts (RHAMM- / -). It was found that the peptide inhibited invasion of tumor cells by ~99.86 % at a concentration of 10 μg / ml (2 × 10–7 M).Conclusions . The obtained results indicate that the peptide RYQLHPYR has antitumor activity and, therefore, has a therapeutic potential for the treatment of prostate cancer.
Introduction . Insulin-like growth factors (IGF) are one of the widely studied factors in oncology. For tumors with a high expression level of IGF typical postoperative relapse, they are invasive and give distant metastases. There are also data on the participation of IGF in the emergence of resistance to anticancer drugs. The mechanisms that determine the influence of insulin-like growth factors on the progression of a number of malignant neoplasms remain undisclosed and carrying out fundamental research in this direction is relevant. Objective: to study the role of IGF type 1 (IGF-1) in multiple myeloma (MM).Materials and methods . 26 samples of bone marrow aspirates received from 26 patients – 14 men and 12 women – were studied in the work. All patients were diagnosed with stage III ММ. The age of patients ranged from 52 to 72 years. From the obtained bone marrow aspirates, using centrifugation in the Ficoll gradient, a mononuclear fraction of bone marrow cells containing plasma cells was obtained. Then we carried out the procedure of extracting RNA and using polymerase chain reaction with reverse transcription, we studied the expression of mRNA of the genes of IGF-1 and MDR1/ABCB1.Results . The paper analyzes the overall survival (OS) of patients with MM depending on the expression of the gene IGF-1. It is shown that for patients with MM who have a high level of IGF-1 expression, a decrease in OS is characteristic and, conversely, with a weak expression of IGF-1 or in the absence of its expression, an increase in OS is observed. Studies of expression of IGF-1 gene and MDR1/ABCB1 gene responsible for the occurrence of multiple drug resistance showed that these genes are co-expressed in patients with MM. Conclusion . The obtained results indicate that the high level of IGF-1 gene expression may be a poor prognostic factor in ММ. IGF-1 may participate in regulation of the mechanisms of emergence of multiple drug resistance in patients with MM.
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