scholarly journals Th1 cytokines in conjunction with pharmacological Akt inhibition potentiate apoptosis of breast cancer cells in vitro and suppress tumor growth in vivo

Oncotarget ◽  
2020 ◽  
Vol 11 (30) ◽  
pp. 2873-2888
Author(s):  
Loral Showalter ◽  
Brian J. Czerniecki ◽  
Gary K. Koski
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Th1 Cytokines

Estrogen receptor β represses breast tumor growth and angiogenesis in vivo

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10101-10101
Author(s):  
J. Hartman ◽  
K. Lindberg ◽  
J. Inzunza ◽  
J. Wan ◽  
A. Ström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Cancer Cell Growth ◽  
Breast Cancer Cell Growth ◽  
Angiogenic Effect

10101 Background: Estrogens are well known stimulators of breast cancer cell growth in vitro as well as in vivo. Two different estrogen receptors exist, namely estrogen receptor (ER) α and β. ERα mediates the proliferative effect of estrogen in breast cancer cells and we have earlier shown that ERβ inhibits cell-cycle progression in vitro. Estrogens are well known stimulators of in vivo breast cancer cell growth as well as angiogenesis, and the effect is mediated through ERα. The function of ERβ in this context is not well understood. Methods: We have used ERα-positive T47D breast cancer cells stably transfected with a Tet/Off regulated ERβ expression vector system. The ERβ-inducible tumor cells are studied in vitro as well as in vivo. Results: By transplanting ERβ-inducible breast cancer cells into SCID-mice, we show that ERβ inhibits tumor growth and reduces the volume of established tumors. Furthermore, we show by immunohistochemistry, that the number of blood microvessels in the tumor periphery is decreased by ERβ expression, counteracting the well-known pro-angiogenic effect of ERα. By Western blot analysis on tumor extracts, we show that the concentration of the important pro-angiogenic growth factors VEGF and bFGF, normally expressed by breast tumor cells, is decreased in the ERβ-expressing tumors compared to the normal tumors. To exclude that the observed anti-angiogenic effect is just a result of reduced tumor growth, we incubated Tet/Off regulated ERβ expressing cells in vitro, during non-hypoxic conditions. We found that the expression of ERβ leads to decreased expression of VEGF and PDGFβ at the mRNA and protein-levels. In transient transfection assays, we found estrogen-ERα mediated up regulation of VEGF, PDGFβ and bFGF-promoter activities in T47D cells, and these activities were all suppressed following co-transfection with an ERβ-expression vector. Conclusions: We conclude that ERβ inhibits growth factor expression at transcriptional level in breast cancer cells; taken together, our data indicates that ERβ inhibits growth and angiogenesis of tumors formed by T47D breast cancer cells. This makes ERβ an interesting therapeutic target in breast cancer and perhaps treatment with the newly designed ERβ-selective ligands might work as a new anti-proliferative and anti-angiogenic therapy. No significant financial relationships to disclose.

Ras-Association Domain Family 1C Protein Enhances Breast Tumor Growth in Vivo

2012 ◽  
Vol 5 ◽  
pp. CGM.S9845 ◽  
Author(s):  
Mark E. Reeves ◽  
Robert J. Aragon ◽  
Mariana Alfakhouri ◽  
Shin-Tai Chen ◽  
Nancy Lowen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Growth Promoter ◽  
Domain Family ◽  
Over Expression ◽  
Immunohistochemical Analyses

The Ras association domain family 1 (RASSF1) gene is a Ras effector that plays an important role in carcinogenesis. We have previously shown that silencing of RASSF1C decreases and over-expression of RASSF1C increases cell proliferation, migration, and attenuates apoptosis of breast cancer cells in vitro. To further confirm our working hypothesis that RASSF1C may play a role as a growth promoter, we have tested the growth of human breast cancer cells stably over-expressing RASSF1A or RASSF1C in nude mice. Our studies show that breast cancer cells over-expressing HA-RASSF1A developed significantly smaller tumors and cells over-expressing HA-RASSF1C developed significantly larger tumors compared to control cells expressing the vector back bone. We have confirmed the expression of HA-RASSF1A and HA-RASSF1C in tumor tissue using RT-PCR, western blotting and immunohistochemical analyses using HA-antibody. Together, our previous in vitro and current in vivo findings further support our hypothesis that RASSF1C, unlike RASSF1A, is not a tumor suppressor and rather it appears to function as tumor growth promoter in breast cancer cells.

Polymalic Acid–Based Nanobiopolymer Provides Efficient Systemic Breast Cancer Treatment by Inhibiting both HER2/neu Receptor Synthesis and Activity

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumor Growth Inhibition ◽  
Human Breast ◽  
Akt Phosphorylation

Biodegradable nanopolymers are believed to offer great potential in cancer therapy. Here, we report thecharacterization of a novel, targeted, nanobiopolymeric conjugate based on biodegradable, nontoxic, andnonimmunogenic PMLA [poly(b-L-malic acid)]. The PMLA nanoplatform was synthesized for repetitive systemictreatments of HER2/neu-positive human breast tumors in a xenogeneic mouse model. Various moieties werecovalently attached to PMLA, including a combination of morpholino antisense oligonucleotides (AON) directedagainst HER2/neu mRNA, to block new HER2/neu receptor synthesis; anti-HER2/neu antibody trastuzumab(Herceptin), to target breast cancer cells and inhibit receptor activity simultaneously; and transferrin receptorantibody, to target the tumor vasculature and mediate delivery of the nanobiopolymer through the hostendothelial system. The results of the study showed that the lead drug tested significantly inhibited the growth ofHER2/neu-positive breast cancer cells in vitro and in vivo by enhanced apoptosis and inhibition of HER2/neureceptor signaling with suppression of Akt phosphorylation. In vivo imaging analysis and confocal microscopydemonstrated selective accumulation of the nanodrug in tumor cells via an active delivery mechanism. Systemictreatment of human breast tumor-bearing nude mice resulted in more than 90% inhibition of tumor growth andtumor regression, as compared with partial (50%) tumor growth inhibition in mice treated with trastuzumab orAON, either free or attached to PMLA. Our findings offer a preclinical proof of concept for use of the PMLAnanoplatform for combination cancer therapy.

Activated interferon signaling by down-regulation of CENP-N contributing to inhibited tumor growth in breast cancer

2019 ◽  
Author(s):  
Zhenhua Zhai ◽  
Ye Zhou ◽  
Xing Liu ◽  
Ying Wang ◽  
Yuyang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Interferon Signaling ◽  
Breast Cancer Patients ◽  
Down Regulation ◽  
Key Factor

Abstract Background Centromere proteins (CENPs) are primary components for chromosomal segregation in the mitotic stage. CENP-N is a member of CENPs, and is a key factor for recruitment of other CENPs and formation of a link between the centromere and micro-tubules, which facilitate cell division. Methods In order to clarify the role of CENP-N in breast cancer, RNA sequences data were downloaded from TCGA online database and the CENP-N expression was knocked down in breast cancer cells. Results The results show that the expression of CENP-N was higher in breast cancer comparing with the paracancerous tissues. In breast cancer, patients with high expression of CENP-N have a short-term overall survival compared with low expression of CENP-N. Both in vitro and in vivo, the growth of breast cancer cells was inhibited by down-regulation of CENP-N. In the gene-chip analysis, it reveals that down-regulation of CENP-N is primarily associated with functions of immune response and anti-tumor ef-fects. Of these changed canonical pathways, the activated interferon signaling was the most significant in CENP-N down-regulated breast cancer cells. In the western blot as-say, up-regulated expressions of molecules involved in interferon signaling were also confirmed. Conclusions Our results suggest that CENP-N can be a potential therapeutic target in the treatment of breast cancer, and the involved interferon signaling needs to be mainly fo-cused on. Keywords: CENP-N, Breast cancer, interferon signaling, Tumor growth

scholarly journals Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ziwei Jiang ◽  
Lixia Pei ◽  
Ying Xie ◽  
Qun Ye ◽  
Xiaoqiang Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients ◽  
Tumor Expression

Abstract Background Metastasis is the leading cause of death among breast cancer patients. MicroRNA-134 has been reported to have a tumor-suppressive role in breast cancer. Ruyiping (RYP), a traditional Chinese formula, has been shown with the ability to reduce breast cancer metastasis in pre-clinical studies. This present study was designed to examine whether miR-134 was involved in RYP-inhibited breast cancer metastasis. Methods The expression of SLUG, E-Cadherin, N-Cadherin and miR-134 in MDA-MB-231 and 4 T1 cells treated with RYP or vehicle control were determined by quantitative realtime-PCR and western blot. Invasiveness determined by transwell assay as well as SLUG gene expression determined by qPCR were detected in cells transfected with chemically synthesized miR-134 mimics or inhibitors. BALB/c mice were injected with 4 T1 cells orthotopically and fed with RYP through gavage. Breast tumor growth, metastasis and tumor expression of EMT markers were detected. Results Compared with the control, Ruyiping formula significantly inhibited SLUG-regulated breast cancer cells invasion. MiR-134 was induced by RYP in vitro and in vivo and was able to suppress SLUG by targeting its 3’UTR. RYP suppressed SLUG expression and cell invasion through miR-134. In 4 T1 tumor-bearing mice, RYP significantly inhibited 4 T1 tumor growth and lung metastasis, increased the levels of miR-134 and epithelial marker while decreased the levels of SLUG and mesenchymal marker. Conclusion Our data uncovered that Ruyiping formula exerts an anti-metastatic activity against breast cancer cells by regulating SLUG through miR-134. MiR-134-SLUG axis might be a promising strategy in breast cancer therapy.

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