The antitumor activity of PNA modified vinblastine cationic liposomes on Lewis lung tumor cells: In vitro and in vivo evaluation

Objective: Qingzaojiufei decoction (QD) is an empirical herbal formula from traditional Chinese medicine that is used for the treatment of lung-related diseases. However, the effect of QD on the growth of lung tumor cells has not been investigated. The aim of this study was to examine the antitumor activity of QD in Lewis lung carcinomas (LLC) in vivo and in vitro, and to elucidate the underlying mechanisms. Methods: The LLC cells were used to assess the antitumor activity of QD by Cell Counting Kit-8 assay in vitro. In vivo, mice were randomly assigned to 5 groups (n = 10/group): the model control (MC) group was intragastrically administered physiological saline (0.9% NaCl) twice daily from day 2 after tumor implantation for 2 weeks. The QD groups were intragastrically administered QD twice daily from 2 weeks before to 2 weeks after tumor implantation for 4 weeks. The mRNA levels were detected by quantitative polymerase chain reaction, the proteins expression was determined by immunohistochemistry or western blotting. Results: Compared with the model group, QD showed inhibition of proliferation of LLC cells and reductions in tumor weight and proliferating cell nuclear antigen protein expression. Furthermore, QD up-regulated p53 mRNA expression, and downregulated c-myc and Bcl-2 mRNA expression, while MMP-9, VEGF, and VEGFR protein expression was suppressed. Phosphorylated ERK1/2 levels were also reduced by QD in a dose-dependent manner. Conclusion: Our findings suggest that QD inhibited lung tumor growth and proliferation, by activation of tumor suppressor genes, inactivation of oncogenes, suppressing the potential for invasion and metastasis, and attenuating angiogenesis. The ERK/VEGF/MMPs signaling pathways may play an important role in QD-induced inhibition of malignant tumor cell proliferation.

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ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

Problems in oncology ◽

10.37469/0507-3758-2019-65-5-760-765 ◽

2019 ◽

Vol 65 (5) ◽

pp. 760-765

Author(s):

Margarita Tyndyk ◽

Irina Popovich ◽

A. Malek ◽

R. Samsonov ◽

N. Germanov ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Growth ◽

Tumor Cells ◽

Human Tumor ◽

Significant Inhibition ◽

In Vivo Studies ◽

Ehrlich Carcinoma ◽

In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

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Nanoemulsion loaded with lycobetaine–oleic acid ionic complex: physicochemical characteristics, in vitro, in vivo evaluation, and antitumor activity

International Journal of Nanomedicine ◽

10.2147/ijn.s43892 ◽

2013 ◽

pp. 1959 ◽

Cited By ~ 29

Author(s):

Hui Zhao ◽

Lu ◽

Tao Gong ◽

zhirong zhang

Keyword(s):

Oleic Acid ◽

Antitumor Activity ◽

Physicochemical Characteristics ◽

Ionic Complex ◽

In Vivo Evaluation

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Macrophage Antitumor Activity Induced by the Antigenic Lymphoma L5178Y/DTIC Subline

Tumori Journal ◽

10.1177/030089168206800502 ◽

1982 ◽

Vol 68 (5) ◽

pp. 365-371 ◽

Cited By ~ 3

Author(s):

Ornella Marelli ◽

Alberto Mantovani ◽

Paola Franco ◽

Angelo Nicotin

Keyword(s):

Antitumor Activity ◽

Tumor Cell ◽

Tumor Cells ◽

Peritoneal Macrophages ◽

Leukemic Cells ◽

Target Cells ◽

Tumor Target ◽

Growth Inhibitory

Murine leukemic cells, after in vivo treatment with antineoplastic drugs, have been shown to express new antigenic specificities that were not detectable on parental cells and that were heritable after the withdrawal of drug treatment. A study was conducted of macrophage antitumor activity triggered by LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC. In vitro non-specific inhibition of tumor cell growth was exhibited by spleen and peritoneal macrophages from mice previously challenged with viable LY/DTIC. Peritoneal macrophages from LY/DTIC immune animals showed moderate, although significant lytic activity against unrelated tumor target cells. Supernatants from mixed lymphocyte-tumor cell cultures, in which LY/DTIC immune lymphocytes and LY/DTIC tumor cells had been cultured, rendered normal macrophages non-specifically growth inhibitory for tumor cells.

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In vitro and in vivo evaluation of cationic liposomes containing zoledronic acid as anticancer agent

Nanomedicine Nanotechnology Biology and Medicine ◽

10.1016/j.nano.2015.12.190 ◽

2016 ◽

Vol 12 (2) ◽

pp. 513

Author(s):

Xinjun Cai ◽

Zeng Wang ◽

Congyao Wang ◽

Huijun Zhou ◽

Jianjun Ni ◽

...

Keyword(s):

Zoledronic Acid ◽

Anticancer Agent ◽

Cationic Liposomes ◽

In Vivo Evaluation

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An NKX2-1/ERK/WNT feedback loop modulates gastric identity and response to targeted therapy in lung adenocarcinoma

10.1101/2020.02.25.965004 ◽

2020 ◽

Author(s):

Rediet Zewdu ◽

Elnaz Mirzaei Mehrabad ◽

Kelley Ingram ◽

Alex Jones ◽

Soledad A. Camolotto ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Cells ◽

Lung Tumor ◽

Genetically Engineered ◽

Reciprocal Relationship ◽

Response To Therapy ◽

Response To Treatment ◽

Mek Inhibitors

ABSTRACTCancer cells often undergo lineage switching during their natural progression and in response to therapy. Lung adenocarcinomas (LUADs) exhibit a variety of differentiation states accompanied by dysregulation of lineage-specific transcription factors such as NKX2-1. Loss of NKX2-1 in human and murine LUAD leads to invasive mucinous adenocarcinoma (IMA), a subtype of lung cancer that exhibits pulmonary to gastric transdifferentiation. Human IMAs harbor a distinct spectrum of mutationally activated driver oncogenes compared to LUAD overall, suggesting that the transdifferentiation induced by NKX2-1 loss plays a context-dependent role in LUAD progression. Using genetically engineered mouse models, we find that NKX2-1 is required for optimal BRAFV600E driven lung tumor initiation but is dispensable for growth of established lung tumors. NKX2-1-deficient, BRAFV600E driven tumors morphologically resemble human IMA, have high levels of ERK phosphorylation and exhibit a distinct response to treatment with combined BRAF/MEK inhibitors. Whereas NKX2-1-positive tumor cells enter quiescence when treated with BRAF/MEK inhibitors, residual NKX2-1-negative cells fail to exit the cell cycle in response to the same therapy. Additionally, BRAF/MEK inhibitors induce canonical WNT signaling in NKX2-1-negative lung tumor cells, which is accompanied by cell identity switching within the gastric lineage. Co-inhibition of MAPK and WNT pathways blocked elements of this lineage switch in vitro and interfered with cell cycle changes imposed by MAPK inhibition in vivo. Our data show that there is a complex and reciprocal relationship between lineage specifiers and oncogenic signaling pathways in the regulation of LUAD identity and suggest that lineage switching induced by targeted therapies may confer new therapeutic vulnerabilities.

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Selectively Targeting Tumor Hypoxia with the Hypoxia-Activated Prodrug CP-506

10.21203/rs.3.rs-438613/v1 ◽

2021 ◽

Author(s):

Alexander M.A. van der Wiel ◽

Victoria Jackson-Patel ◽

Raymon Niemans ◽

Ala Yaromina ◽

Emily Liu ◽

...

Keyword(s):

Antitumor Activity ◽

Tumor Cells ◽

Tumor Hypoxia ◽

Human Tumor ◽

Tumor Oxygenation ◽

Antitumor Effects ◽

Wide Range ◽

Hypoxic Tumor

Abstract Background Hypoxia-activated prodrugs (HAPs) are a promising class of antineoplastic agents that can selectively eliminate hypoxic tumor cells. The present study evaluates the hypoxia-selectivity and antitumor activity of CP-506, a DNA alkylating HAP with favorable pharmacological properties. Methods Stoichiometry of reduction, one-electron affinity, and back-oxidation rate of CP-506 were characterized by fast-reaction radiolytic methods. In vitro, 2D monolayer and 3D spheroid and multicellular layer cultures were used to investigate the hypoxia-selectivity of CP-506. In vivo, the causal relationship between tumor oxygenation and antitumor effects of CP-506 was assessed. Mice bearing a range of human tumor xenografts were exposed to CP-506 and tumor growth was monitored. A multivariate linear regression model was used to identify factors associated with CP-506 treatment outcome. Results Net reduction, metabolism, and cytotoxicity of CP-506 were maximally inhibited at oxygen concentrations above 1 µM (0.1% O2). CP-506 demonstrated cytotoxicity selectively in hypoxic 2D and 3D cell cultures with normoxic/anoxic IC50 ratios up to 203. In vivo, the antitumor effects of CP-506 were selective for hypoxic tumor cells and causally related to tumor oxygenation. CP-506 effectively decreased the hypoxic fraction and inhibited growth of a wide range of hypoxic xenografts. Two well-oxygenated models were refractory to treatment despite intrinsic anoxic sensitivity in vitro. A multivariate regression analysis revealed baseline tumor hypoxia and in vitro sensitivity to CP-506 to significantly correlate with treatment response. Conclusions Our results demonstrate that CP-506 selectively sterilizes hypoxic tumor cells and has broad antitumor activity. Our data also indicate that tumor hypoxia and cellular sensitivity to CP-506 are strong determinants of the antitumor effects of CP-506.

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Enhanced Antitumor Activity of Monophosphate Ester Prodrugs of Gemcitabine: In Vitro and In Vivo Evaluation

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2016.02.006 ◽

2016 ◽

Vol 105 (9) ◽

pp. 2966-2973 ◽

Cited By ~ 4

Author(s):

Huixin Qi ◽

Jia Lu ◽

Jiajun Li ◽

Meiyu Wang ◽

Yunting Xu ◽

...

Keyword(s):

Antitumor Activity ◽

In Vivo Evaluation ◽

Ester Prodrugs

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gro-beta, a -C-X-C- chemokine, is an angiogenesis inhibitor that suppresses the growth of Lewis lung carcinoma in mice.

Journal of Experimental Medicine ◽

10.1084/jem.182.6.2069 ◽

1995 ◽

Vol 182 (6) ◽

pp. 2069-2077 ◽

Cited By ~ 86

Author(s):

Y Cao ◽

C Chen ◽

J A Weatherbee ◽

M Tsang ◽

J Folkman

Keyword(s):

Growth Factor ◽

Lung Carcinoma ◽

Lewis Lung Carcinoma ◽

Lung Tumor ◽

Angiogenesis Inhibitor ◽

Endothelial Cell Proliferation ◽

Dependent Manner ◽

Lewis Lung

We have found that two chemokines, recombinant gro-alpha and gro-beta, specifically inhibit growth factor-stimulated proliferation of capillary endothelial cells in a dose-dependent manner, whereas gro-gamma has no inhibitory effect. In vivo, gro-beta inhibits blood vessel formation in the chicken chorioallantoic membrane assay. It is sufficiently potent to effectively suppress basic fibroblast growth factor-induced corneal neovascularization after systemic administration in mice. Further, gro-beta significantly inhibits the growth of murine Lewis lung carcinoma in syngeneic C57B16/J and immunodeficient nude mice without toxicity. In vitro, Lewis lung carcinoma cells are completely insensitive to recombinant gro-beta at high concentrations that significantly inhibit endothelial cell proliferation. This finding supports the conclusion that gro-beta inhibits Lewis lung tumor growth by suppression of tumor-induced neovascularization.

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