Effect of MiR-210 on the Chemosensitivity of Breast Cancer by Regulating JAK-STAT Signaling Pathway

The study is aimed at exploring the effect of microribonucleic acid- (miR-) 210 on the chemosensitivity of breast cancer and its potential molecular mechanism. Cell Counting Kit-8 (CCK-8) was applied to detect the half maximal inhibitory concentration (IC50) of cisplatin (DDP) on cell, and quantitative polymerase chain reaction (qPCR) was carried out to measure the relative expression level of miR-210. The IC50 value of DDP on cells was detected via CCK-8 after downregulating the expression of miR-210 in MCF-7/DDP cells. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) confirmed the effect of themiR-210 downregulation on the apoptosis of drug-resistant MCF-7/DDP cells. Besides, the impacts of the miR-210 downregulation on apoptosis-related proteins and Janus-activated kinase- (JAK-) signal transducer and activator of transcription (STAT) signaling pathway-related proteins were examined by Western blotting. The interaction between miR-210 and the target protein was detected through luciferase activity assay, qPCR, and Western blotting. Drug-resistant MCF-7/DDP cells had significantly stronger resistance to DDP and a remarkably higher expression level of miR-210 than control parental MCF-7 cells ( p < 0.05 ). After the downregulation of the miR-210 expression, MCF-7/DDP cells had markedly reduced resistance but obviously increased sensitivity to DDP ( p < 0.05 ). MiR-210 downregulation increased the apoptosis of MCF-7/DDP cells ( p < 0.05 ). In addition, after miR-210 was knocked down, the expression level of b-cell lymphoma 2 (Bcl-2) was decreased, while the expression levels of Bcl-2-associated X protein (Bax) and cysteinyl aspartate-specific proteinase-3 (caspase-3) were increased. Besides, miR-210 was able to suppress the expression of protein inhibitor of the activated STAT 4 (PIAS4) gene by directly targeting its 3 ′ untranslated region (3 ′ UTR). The expression of miR-210 has a correlation with chemoresistance of breast cancer MCF-7 cells. MiR-210 regulates the JAK-STAT signal transduction pathway by targeting PIAS4, thus exerting an effect on breast cancer chemosensitivity.

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Suppression of cell proliferation and regulation of estrogen receptor alpha signaling pathway by arsenic trioxide on human breast cancer MCF-7 cells

Journal of Endocrinology ◽

10.1677/joe.0.1820325 ◽

2004 ◽

Vol 182 (2) ◽

pp. 325-337 ◽

Cited By ~ 30

Author(s):

SK Chow ◽

JY Chan ◽

KP Fung

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Estrogen Receptor ◽

Arsenic Trioxide ◽

Signaling Pathway ◽

Cell Counting ◽

Breast Cancers ◽

Chemotherapeutic Drug ◽

Protein Levels ◽

Mcf 7

In recent years, breast cancers have aroused much concern. Together with a growing incidence all over the world, the development of drug resistance to tamoxifen, the most commonly prescribed chemotherapeutic drug for breast cancer patients, has highlighted the importance of developing a new chemotherapeutic drug in combating breast cancer. With the aim of treating breast cancers, the anti-tumor effects of arsenic trioxide in MCF-7 cells have been studied. MCF-7 cells are estrogen responsive cells which mimic breast cancers at the early stage. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and direct cell counting were used to measure cell proliferation. The mechanisms of action were elucidated through the measurement of estrogen receptor (ER) binding, mRNA and protein levels of ERalpha and its activity. We have demonstrated that arsenic trioxide was capable of reducing cell survival in MCF-7 cells via the suppression of the estrogen-induced growth stimulatory effects in MCF-7 cells. Arsenic trioxide was shown to suppress the action of estrogen through the regulation of the ERalpha signaling pathway. Arsenic trioxide could down-regulate ERalpha mRNA and protein levels without competing with estrogen for ERalpha binding. Arsenic trioxide also inhibited the transcription activity mediated by the ERalpha signaling pathway and ultimately it down-regulated c-myc protein expression and inhibited cell entry to S phase under estrogen's stimulation. In conclusion, arsenic trioxide could inhibit the growth of MCF-7 cells by reducing the growth stimulatory effect of estrogen. As estrogen is a primary risk factor in promoting the growth of breast tumor cells, the anti-estrogenicity exhibited by arsenic trioxide sheds light on the therapy of breast cancer.

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Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway

Journal of Chinese Integrative Medicine ◽

10.3736/jcim20110511 ◽

2011 ◽

Vol 9 (5) ◽

pp. 533-538 ◽

Cited By ~ 9

Author(s):

ZH Chu

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Breast Cancer Cells ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Phosphatidylinositol 3 Kinase ◽

Proliferation And Apoptosis ◽

Mcf 7 ◽

Phosphatidylinositol 3

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Targeting the JAK/STAT Signaling Pathway for Breast Cancer.

Current Medicinal Chemistry ◽

10.2174/0929867328666201207202012 ◽

2020 ◽

Vol 28 ◽

Author(s):

Fei Shao ◽

Xiaonan Pang ◽

Gyeong Hun Baeg

Keyword(s):

Breast Cancer ◽

Signal Transduction ◽

Signaling Pathway ◽

Signal Transduction Pathway ◽

Breast Cancer Treatment ◽

Review Article ◽

Transduction Pathway ◽

Inhibitory Effects ◽

Stat Proteins ◽

Stat Signaling

Abstract:: Breast cancer is the most common malignant tumor in women worldwide. Traditional ways of treatment, includ-ing radiotherapy and endocrine therapy, for breast cancer have inevitable side effects. In recent decades, targeted therapies for breast cancer have rapidly advanced and shown a promising future. The JAK/STAT signaling pathway has been shown to play important roles in tumorigenesis, maintenance and metastasis of breast cancer. Hence, many small molecule inhibi-tors of JAK and STAT proteins have been developed. These inhibitors exhibit potent inhibitory effects on breast cancer in both cellular and animal models, and even some of them have already been in clinical trials. This review article discussed the JAK/STAT signal transduction pathway in the pathogenesis of breast cancer, and the potential for the application of JAK/STAT inhibitors in breast cancer treatment.

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Influence of the calmodulin antagonist EBB on cyclin B1 and Cdc2-p34 in human drug-resistant breast cancer MCF-7/ADR cells

Chinese Journal of Clinical Oncology ◽

10.1007/s11805-008-0108-1 ◽

2008 ◽

Vol 5 (2) ◽

pp. 108-112 ◽

Cited By ~ 2

Author(s):

Xu Shi ◽

Yanhong Cheng ◽

Linglin Zou ◽

Dongsheng Xiong ◽

Yuan Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Cyclin B1 ◽

Drug Resistant ◽

Calmodulin Antagonist ◽

Mcf 7

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Information from combined 1H and 31P NMR studies of cell extracts: Differences in metabolism between drug-sensitive and drug-resistant MCF-7 human breast cancer cells

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(90)90343-l ◽

1990 ◽

Vol 169 (2) ◽

pp. 383-390 ◽

Cited By ~ 29

Author(s):

Ofer Kaplan ◽

Peter C.M. van Zijl ◽

Jack S. Cohen

Keyword(s):

Breast Cancer ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

31P Nmr ◽

Drug Resistant ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Nmr Studies ◽

Cell Extracts ◽

Mcf 7

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Discussion On The Mechanism of Que In The Treatment of Breast Neoplasms And Immune Prevention And Treatment

10.21203/rs.3.rs-819024/v1 ◽

2021 ◽

Author(s):

Dan Qiu ◽

Xianxin Yan ◽

Xinqin Xiao ◽

Guijuan Zhang ◽

Yanqiu Wang ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

T Cell ◽

Breast Neoplasms ◽

Signaling Pathway ◽

Immune Regulation ◽

Γδ T Cells ◽

Protein Levels ◽

Stat1 Signaling ◽

Mcf 7

Abstract Background: The precancerous disease of breast cancer is an inevitable stage in the emergence and development of breast neoplasms. Breast cancer (BC) is a common malignant tumor in female worldwide. A large number of literatures have proved that, as antitumor drugs, flavonoid compounds can promote proliferation and immune regulation of T cell. Many researchers believe that Quercetin (Que) has great potential in the field of anti-breast cancer. Besides that, γδ T cells are a class of non-traditional T cells, which have long attracted attention due to their potential in immunotherapy. Above all, JAK/STAT1 signaling pathway is closely related to the immunity.MethodsIn the experiment designed in this paper, we first used Que, one of the flavonoids, to screen the target gene. Then, MCF-10A, MCF-10AT, MCF-7 and MDA-MB231 BC cells were co-cultured with Que for 24h and 48h, apoptosis was found in some the cells. We then cultured Que with γδ T cells and found that Que can promote the proliferation of Vδ2 T cell subsets of γδ T cells, thus enhancing the killing effect of γδ T cells. Western blot was use to showed the change of JAK/STAT1 signaling pathway related proteins after the Que was co-cultured with MCF-10AT and MCF-7 for 48h.ResultsNetwork pharmacology has shown that Que related pathways include the JAK/STAT1 signaling pathway and are associated with precancerous breast cancers. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 in a time and concentration-dependent manner. Most importantly, Que can promote the differentiation of γδ T cells into the Vδ2 T cell subpopulation, this means that Que and γδ T cells may play a synergistic role in killing tumor cells and cellular immune regulation. In addition, our results showed that Que can increase in protein levels of IFNγ-R, p-JAK2 and p-STAT1, while the concomitant decrease protein levels of PD-L1.ConclusionsIn conclusion, Que plays a synergistic role in killing BC cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1, and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of BC.

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Potential Metabolite Nymphayol Isolated from Water Lily (Nymphaea stellata) Flower Inhibits MCF-7 Human Breast Cancer Cell Growth via Upregulation of Cdkn2a, pRb2, p53 and Downregulation of PCNA mRNA Expressions

Metabolites ◽

10.3390/metabo10070280 ◽

2020 ◽

Vol 10 (7) ◽

pp. 280

Author(s):

Laila Naif Al-Harbi ◽

Pandurangan Subash-Babu ◽

Manal Abdulaziz Binobead ◽

Maha Hussain Alhussain ◽

Sahar Abdulaziz AlSedairy ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cell Viability ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Kinase Inhibitor ◽

B Cell Lymphoma ◽

Nuclear Antigen ◽

Mrna Levels ◽

Mcf 7

Controlled production of cyclin dependent kinases (CDK) and stabilization of tumor suppressor genes are the most important factors involved in preventing carcinogenesis. The present study aimed to explore the cyclin dependent apoptotic effect of nymphayol on breast cancer MCF-7 cells. In our previous study, we isolated the crystal from a chloroform extract of Nymphaea stellata flower petals and it was confirmed as nymphayol (17-(hexan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-ol) using x-ray diffraction (XRD), Fourier transform infrared (FTIR), and mass spectroscopy (MS) methods. The cytotoxic effect of nymphayol on MCF-7 cells were analyzed using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The cellular and nuclear damage was determined using propidium iodide (PI) and acridine orange/ethidium bromide (AO/ErBr) staining. Tumor suppressor and apoptosis related mRNA transcript levels were determined using real-time polymerase chain reaction (RT-PCR). Nymphayol potentially inhibits MCF-7 cell viability up to 78%, and the IC50 value was observed as 2.8 µM in 24 h and 1.4 µM in 48 h. Treatment with nymphayol significantly increased reactive oxygen species (ROS) level and the tunnel assay confirmed DNA damage. We found characteristically 76% apoptotic cells and 9% necrotic cells in PI and AO/ErBr staining after 48 h treatment with 2.8 µM of nymphayol. Gene expression analysis confirmed significantly (p ≤ 0.001) increased mRNA levels of cyclin dependent kinase inhibitor 2A (Cdkn2a), retinoblastoma protein 2 (pRb2), p53, nuclear factor erythroid 2-factor 2 (Nrf2), caspase-3, and decreased B-cell lymphoma 2 (Bcl-2), murine double minute 2 (mdm2), and proliferating cell nuclear antigen (PCNA) expression after 48 h. Nymphayol effectively inhibited breast cancer cell viability, and is associated with early expression of Cdkn2a, pRb2, and activation of p53 and caspases.

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Anlotinib Inhibits the Growth of Breast Cancer Cells by Promoting Autophagy and Apoptosis via the Akt/GSK-3α Signalling Pathway

10.21203/rs.3.rs-97756/v1 ◽

2020 ◽

Author(s):

shuyi chen ◽

Ping Zhu ◽

Xue Wang ◽

Youping Jin ◽

Xiuling Zhi ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Lines ◽

Kinase Inhibitor ◽

Underlying Mechanism ◽

Cell Counting ◽

Tunel Staining ◽

Western Blots ◽

Qrt Pcr ◽

Mcf 7

Abstract Background: Anlotinib, a multi-target tyrosine kinase inhibitor, has already been indicated to have significant anticancer effects on lung cancer, colon cancer and ovarian cancer in a phase II clinical trial, but its effect on breast cancer (BC) has not been adequately investigated. Methods: The proliferation activity of BC cell lines MCF-7 and MDA-MB-231 with the treatment of anlotinib was tested by Cell Counting Kit-8 (CCK-8) assay and immunocytochemistry (ICC) staining. We investigated the alteration of cell cycle and apoptosis and autophagy level and the underlying mechanism in the cell lines by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), Western blots, ICC and TUNEL staining and flow cytometry. Further, AT-3 cells were subcutaneously injected into C57BL/6 mice, followed by anlotinib intragastrically. The extracted tumours were assessed by qRT-PCR, Western blots and immunohistochemistry.Results: We found that anlotinib suppressed the cell viability and proliferation of MCF-7 and MDA-MB-231 cell lines and tumour growth in BC xenografts in mice, likely due to abnormal cell cycle arrest and induction of autophagy and apoptosis. Then, we further examined the underlying mechanism of anlotinib, and the results indicated that anlotinib induced apoptosis by promoting autophagy in MCF-7 and MDA-MB-231 cells by regulating the Akt/GSK-3α pathway. The analysis of data from patients with BC collected in TCGA revealed that increased VEGFA expression was related to BC.Conclusions: Our study demonstrated that anlotinib inhibited the growth of BC cells via promoting apoptosis through autophagy mediated by Akt/GSK-3α signalling and may be an effective new drug for BC treatment.

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