scholarly journals Suppression of MD2 Inhibits Breast Cancer in Vitro and in Vivo

2021 ◽  
Author(s):  
Shurong Zheng ◽  
Weida Fu ◽  
Ruimin Ma ◽  
Qidi Huang ◽  
Junwei Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Normal Breast ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Breast Cells ◽  
4T1 Cells ◽  
Mcf 7

Abstract Background: To explore the effects of the intervening measure targeting myeloid differentiation 2 (MD2) on breast cancer progression in vitro and in vivo. Methods: The expression of MD2 in normal breast cells (Hs 578Bst) and three kinds of breast carcinoma cell lines (MCF-7, MDA-MB-231s and 4T1) were detected by western blot. MTT assay was used to detect the proliferation of 4T1 cells treated by L6H21, cell migration and invasion was measured by wound healing assay and transwell matrigel invasion assay, respectively. In addition, to further study the role of MD2 in tumor progression, we assessed the effects of inhibition of MD2 on the progression of xenograft tumors in vivo.Results: The expression of MD2 is much higher in MDA-MB-231s and 4T1cells than that in normal breast cells (Hs 578Bst) or MCF-7 cells (P <0.05). In vitro, suppression of MD2 by L6H21 has a significant inhibition of proliferation, migration and invasion in 4T1 cells in dose-dependent manner. In vivo, L6H21 pretreatment significanly improved survival of 4T1-bearing mice (P <0.05). Additionally, we also observed that there was none of the mice died from the toxic of 10 mg·kg−1 L6H21 in 60 days. Conclusion: Overall, this work indicates that suppression of MD2 shows progression inhibition in vitro and significantly prolong survival in vivo. These findings provide the potential experimental evidence for using MD2 as a therapeutic target of breast carcinoma.

scholarly journals Suppression of MD2 inhibits breast cancer in vitro and in vivo

2021 ◽  
Author(s):  
S. Zheng ◽  
W. Fu ◽  
R. Ma ◽  
Q. Huang ◽  
J. Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Normal Breast ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Breast Cells ◽  
4T1 Cells ◽  
Mcf 7

Abstract Purpose To explore the effects of the intervening measure targeting myeloid differentiation 2 (MD2) on breast cancer progression in vitro and in vivo. Methods The expression of MD2 in normal breast cells (Hs 578Bst) and three kinds of breast carcinoma cell lines (MCF-7, MDA-MB-231 s and 4T1) were detected by western blot. MTT assay was used to detect the proliferation of 4T1 cells treated by L6H21, cell migration and invasion was measured by wound healing assay and trans-well matrigel invasion assay, respectively. In addition, to further study the role of MD2 in tumor progression, we assessed the effects of inhibition of MD2 on the progression of xenograft tumors in vivo. Results The expression of MD2 is much higher in MDA-MB-231 s and 4T1cells than that in normal breast cells (Hs 578Bst) or MCF-7 cells (p < 0.05). In vitro, suppression of MD2 by L6H21 has a significant inhibition of proliferation, migration and invasion in 4T1 cells in dose-dependent manner. In vivo, L6H21 pretreatment significantly improved survival of 4T1-bearing mice (p < 0.05). Additionally, we also observed that none of the mice died from the toxic effect of 10 mg kg−1 L6H21 in 60 days. Conclusion Overall, this work indicates that suppression of MD2 shows progression inhibition in vitro and significantly prolong survival in vivo. These findings provide the potential experimental evidence for using MD2 as a therapeutic target of breast carcinoma.

scholarly journals VP-128, a novel oestradiol-platinum(II) hybrid with selective anti-tumour activity towards hormone-dependent breast cancer cells in vivo

2009 ◽  
Vol 16 (4) ◽  
pp. 1185-1195 ◽  
Author(s):  
Céline Van Themsche ◽  
Sophie Parent ◽  
Valérie Leblanc ◽  
Caroline Descôteaux ◽  
Anne-Marie Simard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nuclear Accumulation ◽  
Dependent Manner ◽  
Anti Tumour Activity ◽  
Tumour Activity ◽  
Mcf 7

We have previously reported the synthesis of VP-128, a new 17β-oestradiol (E2)-linked platinum(II) hybrid with high affinity for oestrogen receptor α (ERα). In the present study, we have investigated the anti-tumour activity of VP-128 towards breast cancer cells in vitro and in vivo. We used human ERα-positive (MCF-7) and -negative (MDA-MB-468) cells as a model for treatment with increasing doses of VP-128, cisplatin or E2 in vitro and for xenograft experiments in nude mice in vivo. Compared with cisplatin, VP-128 showed markedly improved in vitro and in vivo anti-tumour activity towards ERα-positive MCF-7 breast cancer cells, without increased systemic toxicity. In these caspase-3-deficient cells, treatment with VP-128 overcame weak cellular sensitivity to cisplatin in vitro and in vivo. In these cells, only the hybrid induced apoptosis in an ERα-dependent manner, inactivated both X-linked inhibitor of apoptosis protein and Akt, and induced selective nuclear accumulation of ERα and the expression of ER-regulated genes c-myc and tff1, which was blocked by ERα-specific antagonist ICI 282 780. In the case of ERα-negative MDA-MB-468 cells, VP-128, but not cisplatin, induced nuclear accumulation of apoptosis-inducing factor and inhibited c-myc expression. However, VP-128 did not show enhanced in vivo anti-tumour activity compared with cisplatin. These results reveal two different modes of action for VP-128 in ERα-positive and -negative breast cancer cells, and highlight the promising therapeutic value of this unique E2-platinum hybrid for selective targeting of hormone-dependent cancers.

scholarly journals Tryptanthrin exerts anti-breast cancer effects both in vitro and in vivo through modulating the inflammatory tumor microenvironment

2021 ◽  
Vol 71 (2) ◽  
pp. 245-266
Author(s):  
Qingfang Zeng ◽  
Cairong Luo ◽  
Junlae Cho ◽  
Donna Lai ◽  
Xiangchun Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Colony Formation ◽  
Migration And Invasion ◽  
Mouse Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tumor Tissues ◽  
Mcf 7

AbstractTryptanthrin is an indole quinazoline alkaloid from the indigo-bearing plants, such as Isatis indigotica Fort. Typically, this natural compound shows a variety of pharmacological activities such as antitumor, antibacterial, anti-inflammatory and antioxidant effects. This study was conducted to assess the antitumor activity of tryptanthrin in breast cancer models both in vitro and in vivo, and to explore the important role of the inflammatory tumor microenvironment (TME) in the antitumor effects of tryptanthrin. Human breast adenocarcinoma MCF-7 cells were used to assess the antitumor effect of tryptanthrin in vitro. MTT assay and colony formation assay were carried out to monitor the antiproliferative effect of tryptanthrin (1.56~50.0 μmol L−1) on inhibiting the proliferation and colony formation of MCF-7 cells, respectively. The migration and invasion of MCF-7 cells were evaluated by wound healing assay and Transwell chamber assay, respectively. Moreover, the 4T1 murine breast cancer model was established to examine the pharmacological activity of tryptanthrin, and three groups with different doses of tryptanthrin (25, 50 and 100 mg kg−1) were set in study. Additionally, tumor volumes and organ coefficients were measured and calculated. After two weeks of tryptanthrin treatment, samples from serum, tumor tissue and different organs from tumor-bearing mice were collected, and the enzyme-linked immunosorbent assay (ELISA) was performed to assess the regulation of inflammatory molecules in mouse serum. Additionally, pathological examinations of tumor tissues and organs from mice were evaluated through hematoxylin and eosin (H&E) staining. The expression of inflammatory proteins in tumor tissues was measured by immunohistochemistry (IHC) and Western blotting. Tryptanthrin inhibited the proliferation, migration and invasion of MCF-7 cells, up-regulated the protein level of E-cadherin, and down-regulated those of MMP-2 and Snail, as suggested by the MCF-7 cell experiment. According to the results from in vivo experiment, tryptanthrin was effective in inhibiting tumor growth, and it showed favorable safety without inducing the fluctuations of body mass and organ coefficient (p > 0.05). In addition, tryptanthrin also suppressed the expression levels of NOS1, COX-2 and NF-κB in mouse tumor tissues, and regulated those of IL-2, IL-10 and TNF-α in the serum of tumor cells-transplanted mice. Tryptanthrin exerted its anti-breast cancer activities through modulating the inflammatory TME both in vitro and in vivo.

scholarly journals High-throughput allelic expression imbalance analyses identify candidate breast cancer risk genes

2019 ◽  
Author(s):  
Mahdi Moradi Marjaneh ◽  
Haran Sivakumaran ◽  
Kristine M Hillman ◽  
Susanne Kaufmann ◽  
Nehal Hussein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regulatory Elements ◽  
Normal Breast ◽  
Allelic Expression ◽  
Allelic Expression Imbalance ◽  
Risk Genes ◽  
Causal Variants ◽  
Breast Cells

ABSTRACTFine-mapping of breast cancer GWAS regions has identified 195 high confidence signals containing more than 5,000 credible causal variants (CCVs). The CCVs are predominantly noncoding and enriched in regulatory elements and thus may confer the risk by altering gene expression in cis. We analyzed allelic expression imbalance (AEI) of genes surrounding known breast cancer signals, using normal breast and breast tumor transcriptome data and imputed genotypes. Fourteen genes, including NTN4, were identified whose expression was associated with CCV genotype. We showed that CCVs at this signal were located within an enhancer that physically interacts with the NTN4 promoter. Furthermore, knockdown of NTN4 in breast cells increased cell proliferation in vitro and tumor growth in vivo. Here, we present the most comprehensive AEI analysis of breast cancer CCVs resulting in identification of new candidate risk genes.

ZBTB7A promotes migration, invasion and metastasis of human breast cancer cells through NF-κB-induced epithelial–mesenchymal transition in vitro and in vivo

2019 ◽  
Vol 166 (6) ◽  
pp. 485-493 ◽  
Author(s):  
Anyun Mao ◽  
Maojian Chen ◽  
Qinghong Qin ◽  
Zhijie Liang ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cancer Tissue ◽  
Mesenchymal Transition ◽  
Mcf 7

Abstract It has been generally confirmed that zinc finger and BTB domain containing 7A (ZBTB7A) plays an important role in the occurrence and progression of malignant tumours, but the promotion or inhibition effect is related to tumour type. The mechanism between ZBTB7A and breast cancer is not well understood, so further research is needed. In this study, we first investigated the expression of ZBTB7A in tissue samples of clinical breast cancer patients, MDA-MB-231, MCF-7 and MCF-10A cells. Second, we overexpressed the ZBTB7A in MCF-7 cells and silenced the ZBTB7A in MDA-MB-231 cells using lentivirus transfection technology, respectively, and verified the effect of ZBTB7A on migration and invasion of breast cancer cell lines through in vitro cell function experiments, such as wound-healing assay, migration and invasion assay, quantitative real time reverse transcriptase (qRT-PCR) and western blot. Then, the correlation between the above influences, epithelial–mesenchymal transition (EMT) and NF-κB was analysed. Finally, in vivo tumour transplantation model in nude mice was established to verified the effect of ZBTB7A on metastasis of breast cancer MDA-MB-231 cells. In conclusion, ZBTB7A is highly expressed in cancer tissue, breast cancer cell line MDA-MB-231 and MCF-7. Meanwhile, the high expression of ZBTB7A may promote cell migration, invasion and tumour metastasis, which may be related to EMT events by regulating NF-κB.

scholarly journals Grape Seed Procyanidins Inhibit the Growth of Breast Cancer MCF-7 Cells by Down-Regulating the EGFR/VEGF/MMP9 Pathway

2021 ◽  
Vol 16 (2) ◽  
pp. 1934578X2199169
Author(s):  
Fan-ting Kong ◽  
Chen-xi He ◽  
Fan-lei Kong ◽  
Su-fen Han ◽  
Xiang-shun Kong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cell Apoptosis ◽  
Growth Factor Receptor ◽  
Grape Seed ◽  
Dependent Manner ◽  
Flow Cytometric Data ◽  
Mcf 7

Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women. However, it is not clear about its effective treatments. As a potential anticancer agent, grape seed procyanidins (GSPs) have been shown to inhibit the proliferation of various cancer cells in vitro and in vivo. In this study, it was shown that GSPs significantly inhibit MCF-7 cell proliferation in a concentration/time-dependent manner. The flow cytometric data clearly demonstrated that GSPs cause cell cycle arrest in the G2/M phase, followed by cell apoptosis. Moreover, it also confirmed that growth inhibition mediated by treatment with GSPs is related to the induction of apoptosis due to p53 elevation, purportedly by inhibition of the epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)/matrix metalloproteinase 9 (MMP9) pathway. Taken together, these findings suggest that GSPs inhibit MCF-7 cells proliferation and induce cell apoptosis by suppressing EGFR/VEGF/MMP9 pathway.

scholarly journals MnTnHex-2-PyP5+, Coupled to Radiation, Suppresses Metastasis of 4T1 and MDA-MB-231 Breast Cancer via AKT/Snail/EMT Pathways

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1769
Author(s):  
Sung-Won Shin ◽  
Changhoon Choi ◽  
Hakyoung Kim ◽  
Yeeun Kim ◽  
Sohee Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Migration And Invasion ◽  
Tumor Growth Inhibition ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
4T1 Cells

Tumor migration and invasion induced by the epithelial-to-mesenchymal transition (EMT) are prerequisites for metastasis. Here, we investigated the inhibitory effect of a mimic of superoxide dismutase (SOD), cationic Mn(III) ortho-substituted N-n-hexylpyridylporphyrin (MnTnHex-2-PyP5+, MnHex) on the metastasis of breast cancer in cellular and animal models, focusing on the migration of tumor cells and the factors that modulate this behavior. Wound healing and Transwell migration assays revealed that the migration of mouse mammary carcinoma 4T1 cells was markedly reduced during the concurrent treatment of MnHex and radiation therapy (RT) compared with that of the control and RT alone. Bioluminescence imaging showed that MnHex/RT co-treatment dramatically reduced lung metastasis of 4T1 cells in mice, compared with the sham control and both single treatments. Western blotting and immunofluorescence showed that MnHex treatment of 4T1 cells reversed the RT-induced EMT via inhibiting AKT/GSK-3β/Snail pathway in vitro, thereby decreasing cell migration and invasion. Consistently, histopathological analyses of 4T1 tumors showed that MnHex/RT reduced Snail expression, blocked EMT, and in turn suppressed metastases. Again, in the human metastatic breast cancer MDA-MB-231 cell line, MnHex inhibited metastatic potential in vitro and in vivo and suppressed the RT-induced Snail expression. In addition to our previous studies showing tumor growth inhibition, this study demonstrated that MnHex carries the ability to minimize the metastatic potential of RT-treated cancers, thus overcoming their radioresistance.

Antiproliferative activity of synthesized some new benzimidazole carboxamidines against MCF-7 breast carcinoma cells

2018 ◽  
Vol 73 (3-4) ◽  
pp. 137-145 ◽  
Author(s):  
Cigdem Karaaslan ◽  
Filiz Bakar ◽  
Hakan Goker
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Benzimidazole Derivatives ◽  
Dependent Manner ◽  
Base Pairs ◽  
Mcf 7

AbstractBreast cancer is the most endemic cause of cancer among women in both developed and developing countries. Benzimidazole derivatives exemplify one of the chemical classes that show strong cytotoxic activity especially against breast cancer cells (MCF-7). Aromatic amidine derivatives are known as a group of DNA interactive compounds that bind minor groove of the genome, especially A-T base pairs, and show significant in vitro and in vivo toxicity toward cancer cells. In light of these studies, some new mono/dicationic amidino benzimidazole derivatives were synthesized and evaluated for cytotoxic activity on cultured MCF-7 breast cancer cells. Some of these compounds have strongly inhibited MCF-7 cell viability in a dose-dependent manner compared with clinically used reference compounds, imatinib mesylate and docetaxel. Among them, 4-[(5(6)-bromo-1H-benzimidazole-2-yl)amino]benzene-1-carboxamidine (30) showed the best inhibitory activity with IC50value of 4.6 nM.

LHRH Targeted Chonderosomes of Mitomycin C in Breast Cancer: An In Vitro/ In Vivo Study

2019 ◽  
Vol 19 (11) ◽  
pp. 1405-1417
Author(s):  
Jaleh Varshosaz ◽  
Nasim Sarrami ◽  
Mahmoud Aghaei ◽  
Mehdi Aliomrani ◽  
Reza Azizi
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Mitomycin C ◽  
Targeted Delivery ◽  
Precipitation Method ◽  
Cancer Drug ◽  
4T1 Cells ◽  
Mcf 7

Background: Mitomycin C (MMC) is an anti-cancer drug used for the treatment of breast cancer with limited therapeutic index, extreme gastric adverse effects and bone marrow suppression. The purpose of the present study was the preparation of a dual-targeted delivery system of MMC for targeting CD44 and LHRH overexpressed receptors of breast cancer. Methods: MMC loaded LHRH targeted chonderosome was prepared by precipitation method and was characterized for their physicochemical properties. Cell cycle arrest and cytotoxicity tests were studied on cell lines of MCF-7, MDA-MB231 and 4T1 (as CD44 and LHRH positive cells) and BT-474 cell line (as CD44 negative receptor cells). The in vivo histopathology and antitumor activity of MMC-loaded chonderosomes were compared with free MMC in 4T1 cells inducing breast cancer in Balb-c mice. Results: MMC loaded LHRH targeted chonderosomes caused 3.3 and 5.5 fold more cytotoxicity on MCF-7 and 4T1 cells than free MMC at concentrations of 100μM and 10μM, respectively. However, on BT-474 cells the difference was insignificant. The cell cycle test showed no change for MMC mechanism of action when it was loaded in chonderosomes compared to free MMC. The in vivo antitumor studies showed that MMC loaded LHRH targeted chonderosomes were 6.5 fold more effective in the reduction of tumor volume than free MMC with the most severe necrosis compared to non-targeted chonderosomes in pathological studies on harvested tumors. Conclusion: The developed MMC loaded LHRH targeted chonderosomes were more effective in tumor growth suppression and may be promising for targeted delivery of MMC in breast cancer.

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