Matrine reversed multidrug resistance of breast cancer MCF-7/ADR cells through PI3K/AKT signaling pathway

Abstract The relationship between estrogen and some types of breast cancer has been clearly established. However, although several studies have demonstrated the relationship between estrogen and glucose uptake via phosphatidylinositol 3-kinase (PI3K)/Akt in other tissues, not too much is known about the possible cross talk between them for development and maintenance of breast cancer. This study was designed to test the rapid effects of 17β-estradiol (E2) or its membrane-impermeable form conjugated with BSA (E2BSA) on glucose uptake in a positive estrogen receptor (ER) breast cancer cell line, through the possible relationship between key components of the PI3K/Akt signaling pathway and acute steroid treatment. MCF-7 human breast cancer cells were cultured in standard conditions. Then 10 nM E2 or E2BSA conjugated were administered before obtaining the cell lysates. To study the glucose uptake, the glucose fluorescent analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose was used. We report an ER-dependent activation of some of the key steps of the PI3K/Akt signaling pathway cascade that leads cells to improve some mechanisms that finally increase glucose uptake capacity. Our data suggest that both E2 and E2BSA enhance the entrance of the fluorescent glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose, and also activates PI3K/Akt signaling pathway, leading to translocation of glucose transporter 4 to the plasma membrane in an ERα-dependent manner. E2 enhances ER-dependent rapid signaling triggered, partially in the plasma membrane, allowing ERα-positive MCF-7 breast cancer cells to increase glucose uptake, which could be essential to meet the energy demands of the high rate of proliferation.

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Inhibition of the PI3K-Akt signaling pathway disrupts ABCG2-rich extracellular vesicles and overcomes multidrug resistance in breast cancer cells

Biochemical Pharmacology ◽

10.1016/j.bcp.2012.01.033 ◽

2012 ◽

Vol 83 (10) ◽

pp. 1340-1348 ◽

Cited By ~ 41

Author(s):

Vicky Goler-Baron ◽

Irina Sladkevich ◽

Yehuda G. Assaraf

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Cancer Cells ◽

Signaling Pathway ◽

Extracellular Vesicles ◽

Breast Cancer Cells ◽

Akt Signaling ◽

Akt Signaling Pathway

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Icariin induces apoptosis in breast cancer MCF-7 cells by regulating the MELK mediated PI3K/AKT signaling pathway

European Journal of Gynaecological Oncology ◽

10.31083/j.ejgo4205144 ◽

2021 ◽

Vol 42 (5) ◽

pp. 957

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Mcf 7

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Effects of Rhizopus Nigricans Exopolysaccharide on Proliferation, Apoptosis, and Migration of Breast Cancer MCF-7 Cells and Akt Signaling Pathway

International Journal of Polymer Science ◽

10.1155/2021/5621984 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Aizhai Xiang ◽

Chen Ling ◽

Wei Zhang ◽

Honggang Chen

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Akt Signaling ◽

Migration And Invasion ◽

Dependent Manner ◽

Akt Signaling Pathway ◽

Rhizopus Nigricans ◽

And Migration ◽

The Impact ◽

Mcf 7

Objective. To study the effect of Rhizopus nigricans exopolysaccharide EPS1-1 on the proliferation, apoptosis, and migration of breast cancer MCF-7 cells. Methods. Human breast cancer MCF-7 cells were cultured in vitro and treated with different concentrations of EPS1-1. The effect of EPS1-1 on cell proliferation was tested by the CCK-8 experiment, and the effect of EPS1-1 on cell apoptosis was determined by flow cytometry. And the scratch test was used to detect the impact of EPS1-1 on cell migration. Western blot then was used to measure the expression changes of related proteins in the Akt signaling pathway. Results. Compared with the control group, treatment with EPS1-1 significantly reduced the proliferation, migration, and invasion ability of MCF-7 cells and promoted the apoptosis of MCF-7 cells in a dose-dependent manner. In terms of the underlying mechanism, EPS1-1 can significantly inhibit the phosphorylation of Akt at threonine 308 and serine 473 and cause the expression changes of downstream proliferation-related genes CCND1 and p21, apoptosis-related genes Bcl-2 and Bax, and migration-related genes Vimentin and E-cadherin in terms of their protein levels. Conclusion. EPS1-1 can inhibit the proliferation, migration, and invasion of breast cancer MCF-7 cells and promote the apoptosis of MCF-7 cells by inhibiting the activation of the Akt signaling pathway. Therefore, EPS1-1 can be used as a potential new drug or adjuvant drug for the treatment of breast cancer.

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Knockdown of lncRNA FOXD2-AS1 Inhibits Proliferation, Migration, and Drug Resistance of Breast Cancer Cells

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/9674761 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Qiaohong Nong ◽

Shaokang Yu ◽

Hui Hu ◽

Xue Hu

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Invasion And Migration ◽

And Migration ◽

Mcf 7

Objective. In order to investigate the effect of lncRNA FOXD2-AS1 on breast cancer cells proliferation, migration, and drug resistance as well as its molecular mechanism. Methods. Real-time PCR was used to detect the expression of breast cancer tissues and cells from patients admitted to our hospital and the expression of lncRNA FOXD2-AS1 in MCF-7/ADR in adriamycin- (ADR-) resistant breast cancer cells. After interfering with or overexpressing lncRNA FOXD2-AS1 in MCF-7/ADR cells, cell proliferation, apoptosis, invasion, and migration were detected using CCK-8, flow cytometry, Transwell assay, and scratch test, respectively. The protein levels of PI3K, p-PI3K, AKT, and p-AKT in the PI3K/AKT signaling pathway were detected by Western blot. Results. lncRNA FOXD2-AS1 was upregulated in breast cancer tissues and cells and increased cell drug resistance to ADR. Downregulation of lncRNA FOXD2-AS1 inhibited invasion and migration of MCF-7/ADR cells, promoted apoptosis, increased chemosensitivity of MCF-7/ADR cells, and inhibited the activity of PI3K/AKT signaling pathway in MCF-7/ADR cells. Conclusions. lncRNA FOXD2-AS1 can promote the proliferation, invasion, migration, and drug resistance of breast cancer cells, inhibit apoptosis, and accelerate the development of breast cancer by positively regulating the PI3K/AKT signaling pathway.

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Molecular Mechanism of Secondary Endocrine Resistance in Luminal Breast Cancer

BioMed Research International ◽

10.1155/2021/6618519 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Minhua Wu ◽

Jinhua Ding ◽

Limu Wen ◽

Yuxin Zhou ◽

Weizhu Wu

Keyword(s):

Breast Cancer ◽

Western Blot ◽

Signaling Pathway ◽

Molecular Mechanism ◽

Endocrine Resistance ◽

Akt Signaling ◽

Luminal Breast Cancer ◽

Akt Signaling Pathway ◽

Secondary Resistance ◽

Mcf 7

Objective. The molecular mechanism of secondary resistance in Luminal breast cancer was studied to provide new ideas for the treatment of breast cancer. Methods. The sensitivity of the downregulation of myeloid leukemia factor 1-interacting proteins (MLF1IP) to Tamoxifen (TAM) was tested by the Cell Counting Kit-8 (CCK-8). The apoptosis of MLF1IP-mediated resistance was analyzed by flow cytometry (FCM) with/without TAM. Western blot was used in detecting various kinds of apoptosis and the expression of the protein related to the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway to study the molecular mechanism of secondary endocrine resistance in Luminal breast cancer. Results. The downregulation of MLF1IP could significantly increase the drug sensitivity of Michigan Cancer Foundation-7 (MCF-7) cells and also inhibit the proliferation of MCF-7 cells under the stimulation of drugs. Western blot results showed that the expression of Bcl-2-associated X (BAX), Caspase3, Caspase7, and Caspase9 proteins increased when MLF1IP was downregulated. The results of the PI3K/AKT signaling pathway revealed that the phosphatase and tensin homolog deleted on chromosome ten (PTEN) protein expression of MCF7-shRNA was higher than that of MCF7-NC cells, while the expression of p-AKT was lower than that of MCF7-NC cells. Conclusions. (1) MLF1IP-related apoptosis resistance plays an essential role in MLF1IP-mediated secondary resistance of breast cancer cells. (2) MLF1IP promotes AKT phosphorylation by inhibiting the PTEN expression, thus activating the PI3K/AKT signaling pathway and causing the secondary resistance of Luminal breast cancer. (3) MLF1IP can be used as a factor to predict the endocrine resistance of Luminal breast cancer.

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