No abstract

Obesity is associated with breast cancer aggressiveness and drug resistance. Although the underlying mechanisms are unknown, recent studies indicated that exosomes have a principal contributory role in obesity‐associated metabolic complications. Hence, we investigated whether obesity can mediate breast cancer progression and resistance to tamoxifen by plasma‐derived‐exosomes from obese women or not. Plasma exosomes isolated from five normal‐weight (N‐Exo) and five obese women (O‐Exo) were characterized for size, zeta potential, and CD63 expression. After the treatment of MCF‐7 cells with N‐Exo and O‐Exo, cell proliferation, migration, invasion as well as levels of MMP‐9 and MMP‐2 were evaluated by the 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, wound healing, transwell, and zymography methods, respectively. For evaluating resistance to tamoxifen, the cell viability, apoptosis, and the p53 protein were evaluated using the MTT assay, flow cytometry, and western blot methods, respectively. Cell proliferation, migration, and invasion were significantly increased in the cells treated with O‐Exo than untreated cells (p = .001, p = .018, p = .034, respectively). Levels of MMP‐2 and MMP‐9 were remarkably increased in the cells treated with O‐Exo in comparison with ones treated with N‐Exo (p = .040, p = .043, respectively). As for resistance to tamoxifen, O‐Exo had significantly the greater anti‐apoptotic effects in comparison with the N‐Exo group (p = .013). Besides, p53 levels were significantly decreased in the cells treated with O‐Exo than ones treated with N‐Exo (p = .045). The cell viability was significantly more in cells treated with O‐Exo in comparison with the cells only treated with tamoxifen (p = .040). Our findings demonstrated that circulating exosomes derived from obese women could lead to tumorigenesis and tamoxifen resistance in breast cancer cells. However, more studies are needed to establish this notion.

Background: Osteosarcoma (OS) is the basic bone neoplasm with lower survival and poor prognosis. It is distinguished by its offensive nature and metastatic potential. The fundamental death source in OS patients is lung metastasis. In addition, the proliferation and cell migration are thus essential for cancer progression, especially for intrusion and transformation. Several studies have illustrated that 1,25-Dihydroxyvitamin D (1,25(OH)2D) has a critical role in the growth and differentiation of bone. However, knowledge about the outcome of 1,25(OH)2D on the progression and incursion of osteosarcoma cells is minimal. Objective: The present study aimed to analyze the effect of different concentrations of 1,25(OH)2D on the multiplication, progression, and intrusion of OS cells and verify the effective doses of 1,25(OH)2D that can decrease the intensity of the disease and improving the prognosis in OS patients. Methods: Saos-2 cells were treated with 1,25(OH)2D (0, 50, 100, and 200 nM) for 48, 72, and 96 hours. Proliferation, invasion, and migration were determined by MTT assay, Transwell assay, and Scratch test, respectively. The levels of c-Myc and FOXO1 proteins were determined by Western blotting. Results: The proliferation, invasiveness, and migration of Saos-2 cells that were treated with 1,25(OH)2D were significantly decreased compared with untreated cells. Although 1,25(OH)2D notably decreased c-Myc protein levels (after 48 and 72 hours), FOXO1 protein levels have been significantly increased after 48 and 72 hours. 1,25(OH)2D and the vitamin D receptor (VDR) suppress c-Myc function through regulating the c-Myc/MXD1 network and providing thus a molecular basis of 1,25(OH)2D related to the cancer-preventive actions. Conclusion: Based on the present results, 1,25(OH)2D by targeting c-Myc and FOXO1 expression displays anti-invasive, anti-migration and anti-proliferative effects on OS cells in vitro. Our findings suggest that effective doses of the 1,25(OH)2D may reduce of the aggressive potential of OS cell line. However, further investigation and clinical trials are needed.

Background: Osteosarcoma (OS) is the most common type of bone malignancy. Many studies have attempted to find the association between microRNAs and cancer-associated processes. Alterations in miRNA expression through genetic or epigenetic changes, impairment of transcription factors, and ectopic expression of miRNAs induce the development and progression of cancer. Although miR-135b has been thoroughly documented as an oncogene in the majority of studies, some controversies remain about the conflicting role of miR-135b as a tumor-suppressor. Objectives: The present study aimed at investigating the oncogenic and/or tumor-suppressing role of miR-135b in human OS. Methods: In this study, 21 OS tissue samples, along with 21 adjacent bone tissues (normal) as control specimens were collected to analyze the expression of miR-135b. The Saos2 cell-line was transiently transfected with the miR-135b mimic and inhibitor to assess its effect on two critical transcription factors, namely FOXO-1 and c-Myc. qRT-PCR was performed to quantify the expression of miR-135b in both OS tissues and the Saos2 cell-line. The MTT, cell migration, and cell invasion assays were used to characterize the miR-135b function. The western blot analysis was carried out to monitor the targets of miR-135b. Finally, the changes in cellular functions such as migration and invasion, following the transfection of miR-135b mimic and inhibitor, were verified. Results: The results showed that in comparison with the adjacent normal bone tissues, the expression of miR-135b was higher in OS tissue samples, which inversely correlated with the expression rate of FOXO-1, whereas the expression of c-Myc had a direct relationship to miR-135b expression. Functionally, the miR-135b mimic led to an increase in cell proliferation, invasion, and migration of OS cancer cells. Conclusions: MiR-135b induces the proliferation and invasion of OS cells by the degradation of FOXO-1 and upregulation of c-Myc.