The Effect of Nano Albumin Combined with Paclitaxel on Drug Resistance of Breast Cancer Through Regulating ATP Binding Cassette Subfamily B Member 1 (ABCB1)

2022 ◽  
Vol 12 (5) ◽  
pp. 964-970
Author(s):  
Tao Liu ◽  
Xiang Wen ◽  
Qi-Jun Zhao ◽  
Ying Bai ◽  
Qing-Gang Tian
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Tumor Growth ◽  
Cell Group ◽  
High Concentration ◽  
Inhibiting Effect ◽  
S Period ◽  
Mcf 7

The paclitaxel is a common-used chemotherapy drug and its combination with nano albumin reduces drug side effect. However, whether nab-paclitaxel affects drug resistance of breast cancer remains unclear. This study intends to discuss the mechanism of drug resistance induced by nab-paclitaxel. The drug resistance of MCF-7/nab-paclitaxel in MCF-7 cell and cell proliferation was detected by MTT along with analysis of ABCB1 expression, cell cycle, and apoptosis. There was stronger drug resistance of nab-paclitaxel in the MCF-7/nab-paclitaxel cell group through be adopted with different concentration of nab-paclitaxel at the 0th hour, 24th hour and 48th hour. There was remarkable abnormal expression of the ABCB1 in the MCF-7/nab-paclitaxel cell group. The si-ABCB1 could release the quantity of the MCF-7/nab-paclitaxel cell blocked at S period. And the si-ABCB1 could reduce the expression of cyclin D1 and CDK2 in the MCF-7/nab-paclitaxel cell notably. But the expression level of p21 was increased when there was high concentration of si-ABCB1. The si-ABCB1 could increase the quantity of the MCF-7/nab-paclitaxel cell at the later period of cell apoptosis notably. The rat’s tumor growth was delayed obviously at the MCF-7/nabpaclitaxel cell group treated by si-ABCB1. But the inhibiting effect of the MCF-7/nab-paclitaxel cell on tumor growth was less. There was stronger drug resistance of cell for the nano albumin combined with paclitaxel. The function of cell proliferation in breast cancer was restrained by the nano albumin combined with paclitaxel mainly through inducing the expression of ABCB1, adjusting the growth of cell cycle and the expression of P21/BCL-2 protein.

Functional and molecular identification of intermediate-conductance Ca2+-activated K+ channels in breast cancer cells: association with cell cycle progression

2004 ◽  
Vol 287 (1) ◽  
pp. C125-C134 ◽  
Author(s):  
Halima Ouadid-Ahidouch ◽  
Morad Roudbaraki ◽  
Philippe Delcourt ◽  
Ahmed Ahidouch ◽  
Nathalie Joury ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Membrane Potential ◽  
Current Density ◽  
Cell Cycle Progression ◽  
G1 Phase ◽  
Cycle Progression ◽  
Mcf 7 ◽  
In Cells

We have previously reported that the hEAG K+ channels are responsible for the potential membrane hyperpolarization that induces human breast cancer cell progression into the G1 phase of the cell cycle. In the present study, we evaluate the role and functional expression of the intermediate-conductance Ca2+-activated K+ channel, hIK1-like, in controlling cell cycle progression. Our results demonstrate that hIK1 current density increased in cells synchronized at the end of the G1 or S phase compared with those in the early G1 phase. This increased current density paralleled the enhancement in hIK1 mRNA levels and the highly negative membrane potential. Furthermore, in cells synchronized at the end of G1 or S phases, basal cytosolic Ca2+ concentration ([Ca2+]i) was also higher than in cells arrested in early G1. Blocking hIK1 channels with a specific blocker, clotrimazole, induced both membrane potential depolarization and a decrease in the [Ca2+]i in cells arrested at the end of G1 and S phases but not in cells arrested early in the G1 phase. Blocking hIK1 with clotrimazole also induced cell proliferation inhibition but to a lesser degree than blocking hEAG with astemizole. The two drugs were essentially additive, inhibiting MCF-7 cell proliferation by 82% and arresting >90% of cells in the G1 phase. Thus, although the progression of MCF-7 cells through the early G1 phase is dependent on the activation of hEAG K+ channels, when it comes to G1 and checkpoint G1/S transition, the membrane potential appears to be primarily dependent on the hIK1-activity level.

scholarly journals Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wataru Goto ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Koji Takada ◽  
Tamami Morisaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Iron Chelator ◽  
Immune Checkpoints ◽  
Mcf 7

Abstract Background Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo. Methods Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined. Results Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone. Conclusions Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

scholarly journals Aptamer-Protamine-siRNA Nanoparticles in Targeted Therapy of ErbB3 Positive Breast Cancer Cells

2020 ◽  
Author(s):  
Xiangshang Xu ◽  
Li Li ◽  
Xiaolan Li ◽  
Deding Tao ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Regression ◽  
Inhibit Tumor Growth ◽  
Mcf 7 ◽  
Positive Breast Cancer

Abstract Background: RNAi-based technology has achieved good results in both in vitro and in vivo applications, and it is expected to become a good genetic treatment for some diseases, especially neoplastic diseases. But there are still many obstacles in the in vivo application, the most important thing is the lack of an efficient and safe carrier.Methods: In this study, we designed and constructed a new siRNA delivery, which was named as aptamer-protamine-siRNA nanoparticle (APR). APR was consisted of ErbB3 aptamer, protamine and siRNA. We used Zeta nanosize to detect the size of APR to verify whether it is a nano-scale compound. We use the FAMRNA to replace the siRNA to detect whether APR could recognize and enter ErbB3 positive MCF-7 cells. The we replaced the siRNA as oncogene suvivin siRNA to detect whether APR could inhibit tumor growth by silence surviving, and replaced siRNA to CDK1 siRNA to detect the cell cycle blocking effect. At last we tested the anticancer effect and safety of APR by carrying survivin siRNA in MCF-7 bearing nude mice. Results: APR was identified as a nanoscale compound. It showed specific targeting for ErbB3-positive MCF-7 cancer cells. APR has demonstrated the characteristics of inhibiting tumor growth by carrying siRNA against oncogene survivin. APR could also block cell cycle of MCF-7 cells by delivering CDK1 siRNAs. In the ErbB3 positive breast cancer xenograft mice model, APR nanoparticles could inhibit tumor growth and cause tumor regression without any toxicity. Conclusions: In both in vivo and in vitro applications, APR nanoparticles could be targeted to recognize and enter ErbB3 positive tumor cells, and play a corresponding role by silencing targeted gene expression. APR nanoparticle is expected to become a good tumor treatment option.

scholarly journals Leptin-regulated gene expression in MCF-7 breast cancer cells: mechanistic insights into leptin-regulated mammary tumor growth and progression

2008 ◽  
Vol 199 (2) ◽  
pp. 221-233 ◽  
Author(s):  
Candida N Perera ◽  
Hwei G Chin ◽  
Nadire Duru ◽  
Ignacio G Camarillo
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Growth Factor ◽  
Tumor Growth ◽  
Mammary Tumor ◽  
Breast Cancer Cells ◽  
Breast Cancer Incidence ◽  
Mammary Tumor Growth ◽  
Apoptotic Genes ◽  
Mcf 7

Obesity is a recently established risk factor for breast cancer incidence and mortality. A characteristic of obesity is elevated circulating levels of adipocyte-derived hormone leptin. Evidence indicates that leptin plays an important role in mammary tumor formation; however, the mechanisms involved are poorly understood. Toward better defining the role of leptin in breast cancer, we describe the identification of leptin-regulated genes in hormone-responsive Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells using a microarray system. More than 64 leptin-regulated genes were identified including those for growth factors, cell cycle regulators, extracellular matrix (ECM) proteins, and genes associated with metastasis. Cell cycle genes up-regulated by leptin include cyclins D and G, cyclin-dependent kinase 2, p21, p27, and p16. Leptin suppressed the expression of transforming growth factor-β , a cell cycle suppressor. Determining the significance of this effect, treatment of MCF-7 cells with TGFB1 abrogated leptin-stimulated proliferation. Leptin up-regulated the expression of connective tissue growth factor, villin 2, and basigin, factors that are associated with ECM and are known to impact tumor growth. Finally, leptin induced the expression of anti-apoptotic genes BCL2 and survivin, and reduced the expression of apoptotic genes. The effect of leptin on MCF-7 survival was evaluated via TUNEL assay and demonstrated a sixfold reduction in apoptosis in leptin-treated cells, compared with controls. These data suggest leptin promotes mammary tumor growth through multiple mechanisms, including regulating the cell cycle, apoptosis, and by modulating the extracellular environment. The identification of leptin-regulated genes begins to provide mechanistic links into the relationship between obesity and breast cancer incidence and morbidity.

scholarly journals Inhibitory effects of iron depletion plus eribulin on the breast cancer microenvironment

2020 ◽  
Author(s):  
Wataru Goto ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Koji Takada ◽  
Tamami Morisaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Iron Chelator ◽  
Immune Checkpoints ◽  
Mcf 7

Abstract Background: Iron is required for the proliferation of cancer cells, and its depletion suppresses tumor growth. Eribulin mesylate (eribulin), a non-taxane microtubule inhibitor, disrupts the tumor microenvironment via vascular remodeling and obstruction of the epithelial-mesenchymal transition (EMT). Herein, we investigated the effects of the iron chelator on tumor-related properties of breast cancer cells and the effects of iron chelator plus eribulin on tumor growth in vivo.Methods: Two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and BT-549, and one hormone-receptor positive breast cancer cell line, MCF-7, were used in our study. Cell proliferation, cell migration, cell cycle position, and gene expression were analyzed via MTT assays, wound-healing assays, flow cytometry, and quantitative real-time-polymerase chain reaction, respectively. For the in vivo experiments, mice with breast cancer xenografts were treated with the inhibitors, alone or together, and tumor volume was determined.Results: Iron chelator inhibited breast cancer cell proliferation and decreased the proportion of S-phase cells. Conversely, it induced hypoxia, angiogenesis, EMT, and immune checkpoints, as determined by quantifying the expression of marker mRNAs in MDA-MB-231 and MCF-7 cells. Eribulin suppressed the expression of the hypoxia and EMT related marker mRNAs in the presence of iron chelator. Iron chelator plus eribulin inhibited tumor growth in vivo to a greater extent than did either inhibitor alone.Conclusions: Although iron chelator induces oncogenic events (hypoxia, angiogenesis, EMT, and immune checkpoints), it may be an effective treatment for breast cancer when administered in combination with eribulin.

scholarly journals GLUTATHIONE AND GLUTAREDOXIN IN ROSCOVITINE-MEDIATED INHIBITION OF BREAST CANCER CELL PROLIFERATION

2017 ◽  
Vol 72 (4) ◽  
pp. 261-267 ◽  
Author(s):  
E. V. Shakhristova ◽  
E. A. Stepovaya ◽  
O. L. Nosareva ◽  
E. V. Rudikov ◽  
V. V. Novitsky
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Mcf 7

Background: Breast tumors are number one cause of cancer morbidity and mortality among women around the world, and Russia is not an exception. Many proteins that control proliferation of immortalized cells are redox-regulated, which is essential for modulating cellular proliferative activity, especially during tumor growth. Studying the role of glutaredoxin and glutathione in cell cycle phase distribution will allow not only to identify the molecular targets regulating cell proliferation, but also to develop methods of diagnosis and targeted therapy of socially sensitive diseases, including breast cancer, in the future.Aims: To evaluate the role of glutathione and glutaredoxin in the molecular mechanisms regulating MCF-7 breast cancer cell proliferation under the effects of roscovitine, a cyclin-dependent protein kinase inhibitor.Materials and methods: The MCF-7 cell line (human breast adenocarcinoma) was used in the study. The cell culture was incubated in the presence and absence of roscovitine in the final concentration of 20 µmol for 18 h. The production of reactive oxygen species, the distribution of cells between cell cycle phases and the amount of Annexin V positive cells were determined using flow cytometry. The concentrations of total, reduced and oxidized glutathione, protein SH groups and protein-bound glutathione were measured by spectrophotometry. The levels of glutaredoxin, cyclin E and cyclin-dependent protein kinases were estimated by Western blotting with monoclonal antibodies.Results: The effects of roscovitine in the MCF-7 cells resulted in cell cycle arrest in G2/М phases with the decreased levels of cyclin E and cyclin-dependent protein kinase 2. It was accompanied by activation of programmed cell death. In tumor cells incubated in the presence of roscovitine, oxidative stress was triggered, which was accompanied by the elevated generation of reactive oxygen species, the decrease in the concentration of reduced glutathione, and the rise in the level of glutaredoxin. It contributed to the increase in protein glutathionylation against the backdrop of the decreased SH group concentration.Conclusions: Breast cancer cell proliferation under the effects of roscovitine is reduced following not only the decrease in the cyclin level and cyclin-dependent protein kinase activity, but also the shift in the intracellular oxidant/antioxidant ratio. Roscovitine-induced oxidative stress in the MCF-7 cells contributed to protein glutathionylation with the changes in the protein structure and functions. It results in impaired cell cycle progression, indicating a possibility to regulate cellular proliferation through modulating functional properties of redox-dependent proteins using the glutathione/glutaredoxin system.

Synergic effect of Na+-K+ ATPaseB1 and adriamycin on inhibition of cell proliferation and reversal of drug resistance in breast cancer MCF-7 cells

2009 ◽  
Vol 28 (8) ◽  
pp. 861-867
Author(s):  
Yan-Yu Qi ◽  
Kai Liu ◽  
Jie Zhang ◽  
Kai Li ◽  
Jing-Jing Ren ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Synergic Effect ◽  
Mcf 7
Sign in / Sign up

Export Citation Format

Share Document