Effect of zoledronic acid and amputation on bone invasion and lung metastasis of canine osteosarcoma in nude mice

Abstract Background: Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the detailed mechanisms of Tan IIA against CRC metastasis are not well explored. Epithelial-to-mesenchymal transition (EMT) exerts an important regulatory role in CRC metastasis, and our previous mechanism studies demonstrated that β-arrestin1 could regulate CRC EMT partly through β-catenin signaling pathway. Therefore, in this work we investigated whether Tan IIA could regulate CRC EMT through β-arrestin1-mediated β-catenin signaling pathway in vivo and in vitro.Methods: The nude mice tail vein metastasis model was established to observe the effect of Tan IIA on CRC lung metastasis in vivo. The lung metastasis was evaluated by living animal imaging and hemaoxylin-eosin staining. The migratory ability of CRC cells in vitro were measured by transwell and wound healing assays. The protein expression and cellular localization of β-arrestin1 and β-catenin were characterized by immunofluorescence staining and western blot. The β-catenin signaling pathway related proteins and EMT associated proteins in CRC cells were detected by western blot and immunohistochemistry. Results: Our results showed that Tan IIA inhibited the lung metastases of CRC cells in vivo and extended the survival time of nude mice. In vitro, Tan IIA increased the expression of E-cadherin, decreased the secretion of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found the mechanism involving in Tan IIA regulating EMT and metastasis, referring to the suppression of β-arrestin1 expression, reduction of β-catenin nuclear localization, thereby the decreased activity of β-catenin signaling. Conclusion: Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway, and provided support for Tan IIA as anti-metastatic agents in CRC.

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APR-246 alone and in combination with a phosphatidylserine-targeting antibody inhibits lung metastasis of human triple-negative breast cancer cells in nude mice

Breast Cancer Targets and Therapy ◽

10.2147/bctt.s208706 ◽

2019 ◽

Vol Volume 11 ◽

pp. 249-259

Author(s):

Yayun Liang ◽

Cynthia Besch-Williford ◽

Matthew T Cook ◽

Anthony Belenchia ◽

Rolf A Brekken ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Lung Metastasis ◽

Triple Negative Breast Cancer ◽

Nude Mice ◽

Breast Cancer Cells ◽

Triple Negative

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Efficacy in Treating Lung Metastasis of Invasive Breast Cancer with Functional Vincristine Plus Dasatinib Liposomes

Pharmacology ◽

10.1159/000480737 ◽

2017 ◽

Vol 101 (1-2) ◽

pp. 43-53 ◽

Cited By ~ 6

Author(s):

Fan Zeng ◽

Rui-Jun Ju ◽

Lei Liu ◽

Hong-Jun Xie ◽

Li-Min Mu ◽

...

Keyword(s):

Breast Cancer ◽

Lung Metastasis ◽

Nude Mice ◽

Invasive Breast Cancer ◽

Metastatic Breast ◽

Current Treatment ◽

Migration And Invasion ◽

Induce Cell Cycle Arrest ◽

M Phase

Background: The metastasis of breast cancer is the leading cause of death, while lung metastasis is a major clinical phenomenon in patients with invasive breast cancer. The current treatment option comprising surgery, radiation, and standard chemotherapy cannot achieve a satisfactory effect on the treatment of lung metastasis of breast cancer. In this study, we report the potential of preventing lung metastasis of invasive breast cancer using the newly developed functional vincristine plus dasatinib liposomes. Methods: The investigations were performed on invasive breast cancer MDA-MB-231 cells in vitro and in lung metastatic model of invasive breast cancer MDA-MB-231 cells in nude mice. Results: The functional drug liposomes were able to induce cell cycle arrest at G2/M phase, induce apoptosis, inhibit adhesion, migration, and invasion of breast cancer cells in vitro, and prevent lung metastasis of breast cancer in nude mice. Conclusion: These findings indicate a potential clinical use of functional vincristine plus dasatinib liposomes for treating metastatic breast cancer.

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Anti-Tumor Effect of Adenovirus-Mediated P53 Gene Therapy on the Growth of Canine Osteosarcoma Transplanted into Nude Mice

Veterinary and Comparative Oncology ◽

10.1111/j.1476-5810.2005.0064u.x ◽

2005 ◽

Vol 3 (1) ◽

pp. 45-46

Author(s):

N. Kanaya ◽

M. Yazawa ◽

M. Mochizuki ◽

R. Nishimura ◽

N. Sasaki ◽

...

Keyword(s):

Gene Therapy ◽

Nude Mice ◽

P53 Gene ◽

Canine Osteosarcoma

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Zoledronic acid cooperates with a cyclooxygenase-2 inhibitor and gefitinib in inhibiting breast and prostate cancer

Endocrine Related Cancer ◽

10.1677/erc.1.01061 ◽

2005 ◽

Vol 12 (4) ◽

pp. 1051-1058 ◽

Cited By ~ 29

Author(s):

Davide Melisi ◽

Rosa Caputo ◽

Vincenzo Damiano ◽

Roberto Bianco ◽

Bianca Maria Veneziani ◽

...

Keyword(s):

Prostate Cancer ◽

Zoledronic Acid ◽

Nude Mice ◽

Antitumor Effect ◽

Kinase Inhibitor ◽

Metastatic Breast ◽

Cyclooxygenase 2 ◽

Cox 2 ◽

Breast And Prostate Cancer

Biphosphonates (BPs) are widely used to inhibit osteoclastic activity in malignant diseases such as bone metastatic breast and prostate carcinoma. Recent studies reported that BPs could also cause a direct antitumor effect, probably due to their ability to interfere with several intracellular signalling molecules. The enzyme cyclooxygenase-2 (COX-2) and the epidermal growth factor receptor (EGFR) play an important role in the control of cancer cell growth and inhibitors of COX-2 and EGFR have shown antitumor activity in vitro and in vivo in several tumor types. We, and others, have previously shown that EGFR and COX-2 may be directly related to each other and that their selective inhibitors may have a cooperative effect. In the present study we have evaluated the combined effect of zoledronic acid, the most potent nitrogen-containing BP, with the COX-2 inhibitor SC-236 and the selective EGFR-tyrosine kinase inhibitor gefitinib, on breast and prostate cancer models in vitro and in xenografted nude mice. We show that combination of zoledronic acid with SC-236 and gefitinib causes a cooperative antitumor effect accompanied by induction of apoptosis and regulation of the expression of mitogenic factors, proangiogenic factors and cell cycle controllers both in vitro and in xenografted nude mice. The modulatory effect on protein expression and the inhibitory effect on tumor growth is much more potent when the three agents are used together. Since studies are ongoing to explore the antitumor effect of zoledronic acid, our results provide new insights into the mechanism of action of these agents and a novel rationale to translate this feasible combination treatment strategy into a clinical setting.

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Effect of Dietary Fat on Human Breast Cancer Growth and Lung Metastasis in Nude Mice

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/84.2.127 ◽

1992 ◽

Vol 84 (2) ◽

pp. 127-127

Author(s):

D. L. LONGO

Keyword(s):

Breast Cancer ◽

Lung Metastasis ◽

Nude Mice ◽

Dietary Fat ◽

Human Breast Cancer ◽

Cancer Growth ◽

Human Breast ◽

Breast Cancer Growth

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Tissue plasminogen activator and the development of spontaneous lung metastasis in nude mice hosts of transplanted human lung cancer cells.

Haigan ◽

10.2482/haigan.28.843 ◽

1988 ◽

Vol 28 (7) ◽

pp. 843-847

Author(s):

Noriyuki Sagara ◽

Keiji Nakano ◽

Haruhiko Inufusa ◽

Satoshi Hara ◽

Masuo Aizawa ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Lung Metastasis ◽

Nude Mice ◽

Human Lung ◽

Human Lung Cancer ◽

Human Lung Cancer Cells ◽

Tissue Plasminogen

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Functional oral nanoparticles for delivering silibinin and cryptotanshinone against breast cancer lung metastasis

Journal of Nanobiotechnology ◽

10.1186/s12951-020-00638-x ◽

2020 ◽

Vol 18 (1) ◽

Cited By ~ 3

Author(s):

Ying Liu ◽

Xingmei Xie ◽

Xuefeng Hou ◽

Junyi Shen ◽

Jiangpei Shi ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Lung Metastasis ◽

Nude Mice ◽

Oral Bioavailability ◽

Hybrid Nanoparticles ◽

Oral Drug ◽

Nude Mouse Model ◽

Tumor Bearing

Abstract Background Breast cancer lung metastasis occurs in more than 60% of all patients with breast cancer, and most of those afflicted by it eventually die of recurrence. The tumor microenvironment plays vital roles in metastasis. Modulating the tumor microenvironment via multiple pathways could efficiently prevent or inhibit lung metastasis. Silibinin and cryptotanshinone are natural plant products that demonstrate anti-metastasis effects and modulate the tumor microenvironment via different pathways. However, they have poor aqueous solubility, membrane permeability, and oral bioavailability. Oral drug administration may help improve the quality of life and compliance of patients with breast cancer, primarily under long-term and/or follow-up therapy. Herein, we developed poly-N-(2-hydroxypropyl) methacrylamide (pHPMA)-coated wheat germ agglutinin-modified lipid-polymer hybrid nanoparticles, co-loaded with silibinin and cryptotanshinone (S/C-pW-LPNs). We assessed their oral bioavailability, and evaluated their anti-metastasis efficacy in a 4T1 breast cancer tumor-bearing nude mouse model. Results An in vitro mucus diffusion study revealed that pHPMA enhanced W-LPN mucus penetration. After oral administration, pHPMA enhanced nanoparticle distribution in rat jejunum and substantially augmented oral bioavailability. S/C-W-LPNs markedly increased 4T1 cell toxicity and inhibited cell invasion and migration. Compared to LPNs loaded with either silibinin or cryptotanshinone alone, S/C-pW-LPNs dramatically slowed tumor progression in 4T1 tumor-bearing nude mice. S/C-pW-LPNs presented with the most robust anti-metastasis activity on smooth lung surfaces and mitigated lung metastasis foci. They also downregulated tumor microenvironment biomarkers such as CD31, TGF-β1, and MMP-9 that promote metastasis. Conclusions Silibinin- and cryptotanshinone-co-loaded pW-LPNs efficiently penetrate intestinal barriers, thereby enhancing the oral bioavailability of the drug loads. These nanoparticles exhibit favorable anti-metastasis effects in breast cancer-bearing nude mice. Hence, S/C-pW-LPNs are promising oral drug nanocarriers that inhibit breast cancer lung metastasis.

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