TGFBI expression reduces in vitro and in vivo metastatic potential of lung and breast tumor cells

Triple-negative breast cancer (TNBC) is considered to be the most aggressive and malignant neoplasm and is highly metastatic in nature. In the current study, we investigated the anti-metastatic potential of atovaquone, a protozoal drug prescribed for Pneumocystis pneumonia. We showed that atovaquone induced apoptosis and reduced the survival of several aggressive metastatic TNBC cell lines including metastatic patient-derived cells by reducing the expression of integrin α6, integrin β4, FAK, Src, and Vimentin. In order to study the efficacy of atovaquone in suppressing metastasized breast tumor cells in brain and lungs, we performed three in vivo experiments. We demonstrated that oral administration of 50 mg/kg of atovaquone suppressed MDA-MB-231 breast tumor growth by 90% in lungs in an intravenous metastatic tumor model. Anti-metastatic effect of atovaquone was further determined by intracardiac injection of 4T1-luc breast tumor cells into the left ventricle of mouse heart. Our results showed that atovaquone treatment suppressed the growth of metastatic tumors in lungs, liver and brain by 70%, 50% and 30% respectively. In an intracranial model, the growth of HCC1806-luc brain tumors in atovaquone treated mice was about 55% less than that of control. Taken together, our results indicate the anti-metastatic effects of atovaquone in vitro and in vivo in various breast tumor metastasis models.

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Antiproliferative Effect of Electric Fields on Breast Tumor Cells In Vitro and In Vivo

Indonesian Journal of Cancer Chemoprevention ◽

10.14499/indonesianjcanchemoprev6iss3pp71-77 ◽

2017 ◽

Vol 6 (3) ◽

pp. 71 ◽

Cited By ~ 1

Author(s):

Firman Alamsyah ◽

Izzatun Niswah Ajrina ◽

Fitriya Nur Annisa Dewi ◽

Diah Iskandriati ◽

Silvia Arin Prabandari ◽

...

Keyword(s):

Growth Inhibition ◽

Tumor Cells ◽

Breast Tumor ◽

Breast Tissue ◽

In Vitro Study ◽

Mammary Glands ◽

Breast Tumor Cells ◽

Mcf 7

Our research focused on the antiproliferative effect of low intensity (18 Vpp) and intermediate frequency (100 KHz) electrostatic wave between two capacitive electrodes on breast tumor cells in vitro and in vivo. In vitro study has been conducted by using MCF-7 cell lines treated with external electrostatic for 24, 48, and 72 hours of treatment and the cells number were calculated during treatment by using hemocytometer and presented as Growth Inhibition (GI)% efficacy. For in vivo, we used female mice (Mus musculus) strain C3H as animal model. The mice were injected with either MCF-7 cells, mammary tumor cells from C3H donor, or NaCl 0.9% (placebo) subcutaneously into the axilla area and exposed by external electrostatic in each cage for 12 hours in 2 weeks before necropsied. The adjacent and breast tissue were collected and stained with Hematoxylin – Eosin then analyzed for histopathological profile. In vitro study revealed the number of exposed cells decreased with lower proliferation rate than the non-exposed cells. Moreover, the external electrostatic caused 28-39% growth inhibition efficacy of MCF-7 cells. After 2 weeks of exposure, placebo mice were physically normal, whereas the tumor undergone significant shrinkage of more than 67% in size. Histopathological analysis of the mammary glands indicated infiltration of macrophages into the tumor area through the blood vessel. No abnormality was found in the skin layer and mammary glands of the breast tissue of placebo mice. Here, we present new knowledge of electro-capacitive cancer therapy (ECCT) as a novel treatment modality.Keywords : ECCT, tumor, in vitro, in vivo, breast cancer cells, antiproliferative

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Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy—a preclinical study using a syngeneic breast cancer model

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-020-05054-9 ◽

2020 ◽

Author(s):

Patrycja Guzik ◽

Klaudia Siwowska ◽

Hsin-Yu Fang ◽

Susan Cohrs ◽

Peter Bernhardt ◽

...

Keyword(s):

Tumor Growth ◽

Survival Time ◽

Tumor Cells ◽

Median Survival ◽

Breast Tumor ◽

Median Survival Time ◽

Therapy Outcome ◽

Minor Effect

Abstract Purpose It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [177Lu]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy. Methods In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [177Lu]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [177Lu]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 × 200 μg; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment. Results [177Lu]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [177Lu]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [177Lu]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls. Conclusion Application of [177Lu]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates.

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Chemoprotection by VEGF: Rationale for combination nab-paclitaxel and bevacizumab

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1064 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1064-1064 ◽

Cited By ~ 1

Author(s):

V. Trieu ◽

S. Ran ◽

C. Bivens ◽

N. Desai

Keyword(s):

Protective Effect ◽

Tumor Cells ◽

Breast Tumor ◽

T Test ◽

Receptor Expression ◽

Vegf Receptor ◽

Vegf Expression ◽

Clonogenic Assays

1064 Background: Nanoparticle albumin-bound (nab-) paclitaxel (ABX) has shown greater efficacy and less toxicity than solvent-based paclitaxel (TAX) in xenograft models and clinical trials. The goal of this study was to determine the effects of VEGF modulation in human MDA-MB-231 breast tumor cell line and the effects of ABX and VEGF-neutralizing antibody bevacizumab (AVA) combination on the growth and metastasis of orthotopically implanted MDA-MB-231 tumors. Methods: VEGF expression was evaluated by ELISA in MDA-MB-231 tumor extract one week after treatment (qdx5) with saline, doxorubicin (10 mg/kg), TAX (10 mg/kg), or ABX (15 mg/kg). VEGF-receptor expression in MDA-MB-231 was quantitated by RT-PCR. MDA-MB-231 cytotoxicity with ABX, VEGF, AVA alone or in combination was measured by cytotoxicity and clonogenic assays. Implanted MDA-MB-231 tumors expressing luciferase were treated with saline, 2 cycles of ABX (10 mg/kg, two qdx5 cycles separated by 1 week, N=5) alone or in combination with AVA (2, 4 and 8 mg/kg, 2/wkx6). Tumor lymph node and pulmonary metastasis was determined by measuring luciferase activity. Results: Compared with saline, MDA-MB-231 tumors following chemotherapies exhibited significant tumor shrinkage (p≤0.006, t-test) and VEGF induction (p<0.0001, t-test). MDA-MB-231 was shown to express VEGFR2. Exogenous VEGF had a protective effect on MDA-MB-231 tumor cells by reducing cytotoxicity of ABX in both cytotoxicity and clonogenic assays. Sequestration of VEGF with AVA increased cytotoxicity of ABX in vitro. Treatment of MDA-MB-231 breast tumors with ABX and AVA combination resulted in greater than additive antitumor response and significantly reduced metastasis to the lungs (p=0.025 vs control) and LN (p=0.022) at the highest AVA dose. Conclusions: Chemotherapies induced VEGF expression in MDA-MD-231 breast tumor in vivo. In vitro, VEGF exerted a protective effect against ABX chemotherapy in VEGFR2-expressing MDA-MD-231 cells, which was abrogated by addition of AVA. In vivo, ABX and AVA combination significantly inhibited the metastatic potential of MDA-MB-231 tumor cells. These data provide a rational basis for the combination of nab- paclitaxel and bevacizumab in VEGF-receptor expressing tumors. [Table: see text]

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