Nowadays, although chemotherapy is an established therapy for breast cancer, the molecular mechanisms of chemotherapy resistance in breast cancer remain poorly understood. This study aims to explore the effects of endoplasmic reticulum stress on autophagy, apoptosis, and chemotherapy resistance in human breast cancer cells by regulating PI3K/AKT/mTOR signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect the cell viability of six human breast cancer cell lines (MCF-7, ZR-75-30, T47D, MDA-MB-435s, MDA-MB-453, and MDA-MB-231) treated with tunicamycin (5 µM), after which MCF-7 cells were selected for further experiment. Then, MCF-7 cells were divided into the control (without any treatment), tunicamycin (8 µ), BEZ235 (5 µ), and tunicamycin + BEZ235 groups. Cell viability of each group was testified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Western blotting was applied to determine the expressions of endoplasmic reticulum stress and PI3K/AKT/mTOR pathway–related proteins and autophagy- and apoptosis-related proteins. Monodansylcadaverine and Annexin V–fluorescein isothiocyanate/propidium iodide staining were used for determination of cell autophagy and apoptosis. Furthermore, MCF-7 cells were divided into the control (without any treatment), tunicamycin (5 µM), cisplatin (16 µM), cisplatin (16 µM) + BEZ235 (5 µM), tunicamycin (5 µM) + cisplatin (16 µM), and tunicamycin (5 µM) + cisplatin (16 µM) + BEZ235 groups. Cell viability and apoptosis were also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Annexin V–fluorescein isothiocyanate/propidium iodide staining. In MCF-7 cells treated with tunicamycin, cell viability decreased significantly, but PEAK, eIF2, and CHOP were upregulated markedly and p-PI3K, p-AKT, and p-MTOR were downregulated in dose- and time-dependent manners. In the tunicamycin + BEZ235 group, the cell viability was lower and the apoptosis rate was higher than those of the control and monotherapy groups. Compared with the cisplatin group, the tunicamycin + cisplatin group showed a relatively higher growth inhibition rate; the growth inhibition rate substantially increased in the tunicamycin + cisplatin + BEZ235 group than the tunicamycin + cisplatin group. The apoptosis rate was highest in tunicamycin + cisplatin + BEZ235 group, followed by tunicamycin + cisplatin group and then cisplatin group. Our study provide evidence that endoplasmic reticulum stress activated by tunicamycin could promote breast cancer cell autophagy and apoptosis and enhance chemosensitivity of MCF-7 cells by inhibiting the PI3K/AKT/mTOR signaling pathway.
Summary Normal aging is characterized with a decline in hippocampal memory functions that is associated with changes in long‐term potentiation ( LTP ) of the CA 3‐to‐ CA 1 synapse. Age‐related deficit of the dopaminergic system may contribute to impairment of CA 1 LTP . Here we assessed how the modulation of CA 1 LTP by dopamine is affected by aging and how it is dependent on the Ca 2+ source. In slices from adult mice, the initial slope of the field potential showed strong LTP , but in slices from aged mice LTP was impaired. Dopamine did not affect LTP in adult slices, but enhanced LTP in aged slices. The dopamine D1/D5 receptor (D1R/D5R) agonist SKF ‐81297 did not affect LTP in adult but caused a relative small increase in LTP in aged slices; however, although there was no difference in dopamine D4 receptor (D4R) expression, the D4R agonist PD 168077 increased LTP in aged slices to a magnitude similar to that in adult slices. The N ‐Methyl‐D‐aspartate receptor antagonist D‐ AP 5 reduced LTP in adult slices, but not in aged slices. However, in the presence of D‐ AP 5, PD 168077 completely blocked LTP in aged slices. The voltage‐dependent calcium channel ( VDCC ) blocker nifedipine reduced LTP in adult slices, but surprisingly enhanced LTP in aged slices. Furthermore, in the presence of nifedipine, PD 168077 caused a strong enhancement of LTP in aged slices to a magnitude exceeding LTP in adult slices. Our results indicate that the full rescue of impaired LTP in aging by the selective D4R activation and that a large potentiation role on LTP by co‐application of D4R agonist and VDCC blocker may provide novel strategies for the intervention of cognitive decline of aging and age‐related diseases.
Repopulation of decellularized vascular scaffolds (DVS) is limited because of change in the repertoire and ratios of the remaining extracellular matrix (ECM) proteins, for example, loss of glycoproteins and the retention of type I collagen. Pre-treatment of DVS with defined ECM proteins, which match the repertoire of integrin receptors expressed by the embryonic stem cells (mESCs) to be seeded, can increase the reseeding efficacy. mESCs mainly express high levels of functional receptors for LM and FN. Reseeding efficiency of DVS with mESCs was very low, but was sigficantly increased (2.5 ± 0.1 fold) by pre-treating the DVS with A549-conditioned media. In addition, pre-treatment with A549-conditioned media led to a more homogeneous distribution of the seeded mESCs throughout the engineered blood vessel as compared to untreated DVS. This paper may promote blood vessel engineering by stressing the importance of matching the cell binding motifs of DVS and the integrin receptor repertoire of seeded cells.
Subsequently to the publication of this paper, while performing a careful re‑examination of the scientific integrity of the data included in their publications, the authors have realized that they inadvertently used the incorrect western blotting images in Fig. 2B of this article, However, still having access to their original data, the authors were able to reassemble Fig. 2 correctly, and the corrected version of this figure is shown below. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree to this Corrigendum. The authors thank the Editor of Molecular Medicine Reports for granting them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published on Molecular Medicine Reports 14: 1709‑1713, 2016; DOI: 10.3892/mmr.2016.5411].
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