scholarly journals Enhanced Anti-Tumor Effect of Folate-Targeted FA-AMA-hyd-DOX Conjugate in a Xenograft Model of Human Breast Cancer

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7110
Author(s):  
Tian-tian Liao ◽  
Jiang-fan Han ◽  
Fei-yue Zhang ◽  
Ren Na ◽  
Wei-liang Ye
Keyword(s):  
Breast Cancer ◽  
Nude Mice ◽  
Folate Receptor ◽  
Xenograft Model ◽  
Maximum Tolerated Dose ◽  
Therapeutic Drug ◽  
Antitumor Effects ◽  
Tumor Bearing

Folate-aminocaproic acid-doxorubicin (FA-AMA-hyd-DOX) was firstly synthesized by our group. It was indicated that FA-AMA-hyd-DOX was pH-responsive, and had strong cytotoxicity on a folate receptor overexpressing cell line (KB cells) in vitro. The aim of our study was to further explore the potential use of FA-AMA-hyd-DOX as a new therapeutic drug for breast cancer. The cellular uptake and the antiproliferative activity of the FA-AMA-hyd-DOX in MDA-MB-231 cells were measured. Compared with DOX, FA-AMA-hyd-DOX exhibited higher targeting ability and cytotoxicity to FR-positive tumor cells. Subsequently, the tissue distribution of FA-AMA-hyd-DOX was studied, and the result confirmed that DOX modified by FA can effectively increase the selectivity of drugs in vivo. After determining the maximum tolerated dose (MTD) of FA-AMA-hyd-DOX in MDA-MB-231 tumor-bearing nude mice, the antitumor effects and the in vivo safety of FA-AMA-hyd-DOX were systematically evaluated. The data showed that FA-AMA-hyd-DOX could effectively increase the dose of DOX tolerated by tumor-bearing nude mice and significantly inhibit MDA-MB-231 tumor growth in vivo. Furthermore, FA-AMA-hyd-DOX treatment resulted in almost no obvious damage to the mice. All the positive data suggest that FA-targeted FA-AMA-hyd-DOX is a promising tumor-targeted compound for breast cancer therapy.

Eradication of Growth of HER2-Positive Ovarian Cancer With Trastuzumab-DM1, an Antibody-Cytotoxic Drug Conjugate in Mouse Xenograft Model

2014 ◽  
Vol 24 (7) ◽  
pp. 1158-1164 ◽  
Author(s):  
Lin Yu ◽  
Yuxi Wang ◽  
Yuqin Yao ◽  
Wenting Li ◽  
Qinhuai Lai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Nude Mice ◽  
Binding Capacity ◽  
Xenograft Model ◽  
Her2 Positive ◽  
Antitumor Effects ◽  
Skov3 Cells

ObjectiveOvarian cancer is 1 kind of a highly malignant gynecologic tumor, and current treatments have not achieved satisfactory effects. Human epidermal growth factor receptor 2 (HER2)–targeted therapies including trastuzumab and trastuzumab-DM1 (T-DM1) (antibody-cytotoxic drug conjugates) have been applied to treat HER2-overexpressing breast cancers in clinic. In the present study, we explored whether T-DM1 could effectively treat HER2-positive human ovarian carcinoma in vitro and in vivo.MethodsHER2 expressions of 6 ovarian cancer cell lines and 2 breast carcinoma cell lines were validated, and the binding capacity of T-DM1 to HER2-positive ovarian cancer SKOV3 cells were analyzed by flow cytometry. Nude mice bearing intraperitoneal and subcutaneous SKOV3 xenografts were used to investigate the antitumor effect of T-DM1.ResultsHigh HER2 expressions in SKOV3 cell lines were detected. The binding capacity of T-DM1 to HER2-positive SKOV3 cells was in a similar manner comparing with trastuzumab. In vitro, T-DM1 showed strong growth inhibitory on SKOV3 cells, with IC50 values of 0.15 nmol/L. Nude mice bearing intraperitoneal and subcutaneous SKOV3 xenografts were used to investigate the antitumor effects of T-DM1 in vivo. In subcutaneous xenografts model, T-DM1 (30 mg/kg and 10 mg/kg) indicated significant anticancer effects. It is noteworthy that tumors were completely eradicated in the T-DM1 (30 mg/kg) group, and no regrowth was observed in a long time after the termination of the treatment. In the peritoneal xenograft model, tumor nodules in 3 of 7 mice were hardly observed in the abdominal cavity of mice after intraperitoneal injection of T-DM1 (30 mg/kg). At the same time, tumor nodules from the other 4 mice weighed on the average of only 0.07 g versus 1.77 g in control group.ConclusionsOur data showed that T-DM1 possessed promising antitumor effects on HER2-overexpressing ovarian cancer in mouse model, which provided valuable references for the future clinical trials.

Recombinant human PDCD5 protein enhances chemosensitivity of breast cancer in vitro and in vivo

2013 ◽  
Vol 91 (6) ◽  
pp. 526-531 ◽  
Author(s):  
Lanlan Wang ◽  
Changjun Wang ◽  
Bingnan Su ◽  
Quansheng Song ◽  
Yingmei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Intraperitoneal Administration ◽  
Xenograft Model ◽  
Cell Types ◽  
Antitumor Effects ◽  
Protein Levels

Resistance to paclitaxel is common for treatment of breast cancer. Programmed cell death 5 (PDCD5) accelerates apoptosis in different cell types in response to various stimuli; moreover PDCD5 has been shown to be down-regulated in many tumors. In this study, protein levels of PDCD5 were found to be up-regulated in paclitaxel-treated MDA-MB-231 breast cancer cells. MTT, CCK-8, and clonogenic assays have shown that recombinant human PDCD5 (rhPDCD5) alone could not produce an obvious growth inhibition. However, upon paclitaxel triggering apoptosis, rhPDCD5 protein potentiated chemotherapeutic drugs-induced growth arrest in MDA-MB-231, SK-BR-3, and ZR-75-1 breast cancer cells. In vivo, we use a human breast cancer xenograft model to study. We found that rhPDCD5 dramatically improves the antitumor effects of paclitaxel treatment by intraperitoneal administration. These data suggest that rhPDCD5 has the potential to use as a therapeutic agent to enhance the paclitaxel sensitivity of breast cancer cells.

scholarly journals Edelfosine nanoemulsions inhibit tumor growth of triple negative breast cancer in zebrafish xenograft model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sofia M. Saraiva ◽  
Carlha Gutiérrez-Lovera ◽  
Jeannette Martínez-Val ◽  
Sainza Lores ◽  
Belén L. Bouzo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Xenograft Model ◽  
Skin Barrier ◽  
Zebrafish Embryos ◽  
Biorelevant Media

AbstractTriple negative breast cancer (TNBC) is known for being very aggressive, heterogeneous and highly metastatic. The standard of care treatment is still chemotherapy, with adjacent toxicity and low efficacy, highlighting the need for alternative and more effective therapeutic strategies. Edelfosine, an alkyl-lysophospholipid, has proved to be a promising therapy for several cancer types, upon delivery in lipid nanoparticles. Therefore, the objective of this work was to explore the potential of edelfosine for the treatment of TNBC. Edelfosine nanoemulsions (ET-NEs) composed by edelfosine, Miglyol 812 and phosphatidylcholine as excipients, due to their good safety profile, presented an average size of about 120 nm and a neutral zeta potential, and were stable in biorelevant media. The ability of ET-NEs to interrupt tumor growth in TNBC was demonstrated both in vitro, using a highly aggressive and invasive TNBC cell line, and in vivo, using zebrafish embryos. Importantly, ET-NEs were able to penetrate through the skin barrier of MDA-MB 231 xenografted zebrafish embryos, into the yolk sac, leading to an effective decrease of highly aggressive and invasive tumoral cells’ proliferation. Altogether the results demonstrate the potential of ET-NEs for the development of new therapeutic approaches for TNBC.

In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effects ◽  
Antiestrogenic Activity ◽  
Er Positive ◽  
In Vivo Effects ◽  
Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

scholarly journals Mibefradil inhibits the proliferation of triple-negative breast cancer by targeting AURKA to regulate apoptosis signal pathway

2021 ◽  
Author(s):  
Xu Han ◽  
Xiujuan Qu ◽  
Beixing Liu ◽  
Yizhe Wang ◽  
Yang Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Molecular Docking ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Therapeutic Drug ◽  
Specific Gene ◽  
In Vivo Models

Abstract Background: Triple negative breast cancer (TNBC) is a tumor characterized by high recurrence and mortality, but without effective targeted therapy. It is urgent to explore new treatment strategy to improve the efficacy of TNBC therapy. Methods: Transcriptomic profiling datasets of TNBC were used for screening TNBC specific gene sets. Drug prediction was performed in Connectivity map (CMap) database. Molecular docking method was used for analyzing drug targets. In vitro and in vivo models of TNBC were constructed to examine the drug efficacy. Results: We screened out Mibefradil, a T-type Ca2+ channel blocker, might be a potential therapeutic drug for TNBC by transcriptomics and bioinformatics analysis, and verified that Mibefradil could inhibit the proliferation of TNBC cells by inducing apoptosis and cell cycle arrest. Furthermore, by network pharmacology and molecular docking analysis, AURKA was predicted as the most possible drug target of Mibefradil. Finally, it was proved that Mibefradil treatment could induce apoptosis by decreasing protein expression and phosphorylation level of AURKA in vitro and in vivo. Conclusions: Mibefradil played anti-cancer role in TNBC cells by targeting to AURKA to induce cell cycle and apoptosis. Our results repurposed Mibefradil as a potential targeted drug of TNBC and provided a fundamental research for a novel strategy TNBC treatment.

Young Barley Indicates Antitumor Effects in Experimental Breast Cancer In Vivo and In Vitro

2016 ◽  
Vol 68 (4) ◽  
pp. 611-621 ◽  
Author(s):  
Peter Kubatka ◽  
Martin Kello ◽  
Karol Kajo ◽  
Peter Kruzliak ◽  
Desanka Výbohová ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Antitumor Effects

Effect of Auraptene on angiogenesis in Xenograft model of breast cancer

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohammad Reza Shiran ◽  
Elham Mahmoudian ◽  
Abolghasem Ajami ◽  
Seyed Mostafa Hosseini ◽  
Ayjamal Khojasteh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Animal Model ◽  
Protein Expression ◽  
Western Blot ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Abstract Objectives Angiogenesis is the most important challenge in breast cancer treatment. Recently, scientists become interesting in rare natural products and intensive researches was performed to identify their pharmacological profile. Auraptene shows helpful effects such as cancer chemo-preventive, anti-inflammatory, anti-oxidant, immuno-modulatory. In this regard, we investigated the anti-angiogenesis effect of Auraptene in in-vitro and in-vivo model of breast cancer. Methods In this study, 4T, MDA-MB-231 and HUVEC cell lines were used. The proliferation study was done by MTT assay. For tube formation assay, 250 matrigel, 1 × 104 HUVEC treated with Auraptene, 20 ng/mL EGF, 20 ng/mL bFGF and 20 ng/mL VEGF were used. Gene expression of important gene related to angiogenesis in animal model of breast cancer was investigated by Real-time PCR. Protein expression of VCAM-1 and TNFR-1 gene related to angiogenesis in animal model of breast cancer was investigated by western-blot. Results Auraptene treatment led to reduction in cell viability of MDA-MB-231 in a concentration-dependent manner. Also, we observed change in the number of tubes or branches formed by cells incubated with 40 and 80 μM Auraptene. Auraptene effect the gene expression of important gene related to angiogenesis (VEGF, VEGFR2, COX2, IFNɣ). Moreover, the western blot data exhibited that Auraptene effect the protein expression of VCAM-1 and TNFR-1. Conclusions Overall, this study shows that Auraptene significantly suppressed angiogenesis via down-regulation of VEGF, VEGFR2, VCAM-1, TNFR-1, COX-2 and up-regulation of IFNγ.

scholarly journals Isoform-specific promotion of breast cancer tumorigenicity by TBX3 involves induction of angiogenesis

2019 ◽  
Vol 100 (3) ◽  
pp. 400-413
Author(s):  
Milica Krstic ◽  
Haider M. Hassan ◽  
Bart Kolendowski ◽  
M. Nicole Hague ◽  
Pieter. H. Anborgh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Transcriptional Analysis ◽  
Breast Cancer Cell Lines ◽  
Tumor Vascularity ◽  
Mouse Xenograft Model

Abstract TBX3 is a member of the highly conserved family of T-box transcription factors involved in embryogenesis, organogenesis and tumor progression. While the functional role of TBX3 in tumorigenesis has been widely studied, less is known about the specific functions of the different isoforms (TBX3iso1 and TBX3iso2) which differ in their DNA-binding domain. We therefore sought to investigate the functional consequence of this highly conserved splice event as it relates to TBX3-induced tumorigenesis. By utilizing a nude mouse xenograft model, we have identified differential tumorigenic potential between TBX3 isoforms, with TBX3iso1 overexpression more commonly associated with invasive carcinoma and high tumor vascularity. Transcriptional analysis of signaling pathways altered by TBX3iso1 and TBX3iso2 overexpression revealed significant differences in angiogenesis-related genes. Importantly, osteopontin (OPN), a cancer-associated secreted phosphoprotein, was significantly up-regulated with TBX3iso1 (but not TBX3iso2) overexpression. This pattern was observed across three non/weakly-tumorigenic breast cancer cell lines (21PT, 21NT, and MCF7). Up-regulation of OPN in TBX3iso1 overexpressing cells was associated with induction of hyaluronan synthase 2 (HAS2) expression and increased retention of hyaluronan in pericellular matrices. These transcriptional changes were accompanied by the ability to induce endothelial cell vascular channel formation by conditioned media in vitro, which could be inhibited through addition of an OPN neutralizing antibody. Within the TCGA breast cancer cohort, we identified an 8.1-fold higher TBX3iso1 to TBX3iso2 transcript ratio in tumors relative to control, and this ratio was positively associated with high-tumor grade and an aggressive molecular subtype. Collectively, the described changes involving TBX3iso1-dependent promotion of angiogenesis may thus serve as an adaptive mechanism within breast cancer cells, potentially explaining differences in tumor formation rates between TBX3 isoforms in vivo. This study is the first of its kind to report significant functional differences between the two TBX3 isoforms, both in vitro and in vivo.

scholarly journals Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2305 ◽  
Author(s):  
Yu-Cheng Chou ◽  
Meng-Ya Chang ◽  
Hsu-Tung Lee ◽  
Chiung-Chyi Shen ◽  
Tomor Harnod ◽  
...  
Keyword(s):  
Nude Mice ◽  
Human Cancer ◽  
Xenograft Model ◽  
Biological Properties ◽  
Migration And Invasion ◽  
Phenethyl Isothiocyanate ◽  
Human Glioblastoma ◽  
Apoptosis Protein

Phenethyl isothiocyanate (PEITC) from cruciferous vegetables can inhibit the growth of various human cancer cells. In previous studies, we determined that PEITC inhibited the in vitro growth of human glioblastoma GBM 8401 cells by inducing apoptosis, inhibiting migration and invasion, and altering gene expression. Nevertheless, there are no further in vivo reports disclosing whether PEITC can suppress the growth of glioblastoma. Therefore, in this study we investigate the anti-tumor effects of PEITC in a xenograft model of glioblastoma in nude mice. Thirty nude mice were inoculated subcutaneously with GBM 8401 cells. Mice with one palpable tumor were divided randomly into three groups: control, PEITC-10, and PEITC-20 groups treated with 0.1% dimethyl sulfoxide (DMSO), and 10 and 20 μmole PEITC/100 μL PBS daily by oral gavage, respectively. PEITC significantly decreased tumor weights and volumes of GBM 8401 cells in mice, but did not affect the total body weights of mice. PEITC diminished the levels of anti-apoptotic proteins MCL-1 (myeloid cell leukemia 1) and XIAP (X-linked inhibitor of apoptosis protein) in GBM 8401 cells. PEITC enhanced the levels of caspase-3 and Bax in GBM 8401 cells. The growth of glioblastoma can be suppressed by the biological properties of PEITC in vivo. These effects might support further investigations into the potential use of PEITC as an anticancer drug for glioblastoma.

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