Metastasis Of Lewis Lung Cancer Research Articles

Huayu Wan Prevents Lewis Lung Cancer Metastasis in Mice via the Platelet Pathway.

Objective To study the mechanism of Huayu Wan on the metastasis of Lewis lung cancer in mice via the platelet pathway. Method Construction of the lung metastasis model by injection of Lewis cells through the tail vein. The next day, 72 mice were randomly divided into the Huayu Wan group (HYW), the aspirin group, the control group, and the normal group . Treatment was given for 5 days per week for a total of 16 days. The size and distribution of lung metastases were observed. Thromboelastography was used to detect platelet function, flow cytometry was used to analyze platelet activation, and ELISA was used to detect platelet tumor metastasis-related factor expression. Result Lung weight in the control group was significantly higher than that in the HYW group (P < 0.05). The distribution of lung metastases in the control group was obviously more than that in the HYW group. The thromboelastogram showed that the R value of the control group was significantly lower than the normal group, while the R values of the HYW and aspirin groups were higher than the control group (P < 0.05). Flow cytometry analysis showed that the expression of CD62P in platelet-rich plasma in the control group was significantly higher than that in the normal group, while the expression of CD62P in the HYW and aspirin groups was lower than that in the control group (P < 0.05). In addition, ELISA showed that the expression of VEGF, bFGF, and CD62P in serum of the HYW group was significantly decreased than the control group (P < 0.05), and the expression of VEGF and bFGF in serum of the aspirin group was significantly decreased than the control group (P < 0.05). Conclusion The mechanism of Huayu Wan inhibiting the metastasis of lung cancer in mice may be related to the improvement of blood hypercoagulability, the inhibition of platelet activation, and the expression of VEGF, bFGF, and CD62P.

Effect of Astragalus Polysaccharide on the Expression of VEGF and EGFR in Mice with Lewis Transplantable Lung Cancer.

The aim of this study was to determine the effect of Astragalus polysaccharide (APS) on the expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in mice with Lewis transplantable lung cancer. It was an experimental study carried out from June 2017 to January 2018 at the College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China. Forty male SPF-level C57BL/6J mice were selected and inoculated with Lewis lung cancer cell suspension in the right axilla of the mice to establish a lung-cancer mouse model. The mice were randomly divided into a model control group and APS groups with high, middle and low dosages, respectively, 10 in each group. After inoculation of Lewis tumor cell suspension for 2 days, mice in the model control group were injected intraperitoneally with 50 mL/kg of 0.9% sodium chloride solution, whereas, mice in the APS groups with high, middle and low dosages were intraperitoneally injected with APS at 100, 50, 25 mg/kg, respectively. The research results showed that APS can effectively inhibit the growth and metastasis of Lewis lung cancer in mice, improve immune organ function, inhibit the protein expression of VEGF and EGFR in tumor tissues, and have a concentration-effect relationships.

Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages

Although M2-like tumor-associated macrophages (TAMs) have been considered as a vital therapeutic target in cancer therapy due to their role in promoting tumor progression and metastasis, very few compounds have been identified to inhibit M2-like polarization of TAMs. Here, we showed that Imatinib significantly prevented macrophage M2-like polarization induced by IL-13 or IL-4 in vitro, as illustrated by reduced expression of cell surface marker CD206 and M2-like genes, including Arg1, Mgl2, Mrc1, CDH1, and CCL2. Further, the migration of lung cancer cells promoted by the conditioned medium from M2-like macrophages could be restrained by Imatinib. Mechanistically, Imatinib inhibited STAT6 phosphorylation and nuclear translocation, resulting in the macrophage M2-like polarization arrest. Furthermore, Imatinib reduced the number of metastasis of Lewis lung cancer without affecting tumor growth. Both in tumor and lung tissues, the percentage of M2-like macrophages decreased after the administration of Imatinib for one week. Taken together, these data suggest that Imatinib is able to inhibit macrophage M2-like polarization, which plays a vital role in Imatinib suppressed metastasis of Lewis lung cancer.

Effects of Astragalus Polysaccharides on Growth, Metastasis and Cell Cycle of Lewis Lung Cancer in Tumor-bearing Mice with Qi and Yin Deficiency

Effects of Astragalus Polysaccharides on Growth, Metastasis and Cell Cycle of Lewis Lung Cancer in Tumor-bearing Mice with Qi and Yin Deficiency

Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages.

Accumulated evidence suggests that M2-like polarized tumor associated macrophages (TAMs) plays an important role in cancer progression and metastasis, establishing TAMs, especially M2-like TAMs as an appealing target for therapy intervention. Here we found that metformin significantly suppressed IL-13 induced M2-like polarization of macrophages, as illustrated by reduced expression of CD206, down-regulation of M2 marker mRNAs, and inhibition of M2-like macrophages promoted migration of cancer cells and endothelial cells. Metformin triggered AMPKα1 activation in macrophage and silencing of AMPKα1 partially abrogated the inhibitory effect of metformin in IL-13 induced M2-like polarization. Administration of AICAR, another activator of AMPK, also blocked the M2-like polarization of macrophages. Metformin greatly reduced the number of metastases of Lewis lung cancer without affecting tumor growth. In tumor tissues, the percentage of M2-like macrophage was decreased and the area of pericyte-coated vessels was increased. Further, the anti-metastatic effect of metformin was abolished when the animals were treated with macrophages eliminating agent clodronate liposome. These findings suggest that metformin is able to block the M2-like polarization of macrophages partially through AMPKα1, which plays an important role in metformin inhibited metastasis of Lewis lung cancer.

Ethanol supports macrophage recruitment and reinforces invasion and migration of Lewis lung carcinoma.

Inflammation plays a critical role in cancer progression, and our data suggested that ethanol (EtOH) could promote the progression of breast cancer via increased monocyte chemo-attractant protein-1 (MCP-1). Thus, we investigated the effects of EtOH on lung cancer growth and metastasis to explore whether immunosuppression had a role. C57BL/6 mice (n=10) implanted with Lewis lung cancer (LLC) cells were used to model physiologically relevant EtOH intake on tumor growth and inflammation after macrophage polarization. Tumors were isolated and measured, and MCP-1 expression was measured via immunohistochemistry and Western blot. Recruitment of macrophages using CD11b and F4/80 antibodies was detected with immunohistochemistry and flow cytometry. Changes in arginase I and inducible nitric oxide synthase (iNOS) expression were measured with immunofluorescent microscopy. EtOH's effect on in vitro tumor angiogenesis was evaluated in culture, and the tumor microvessel density was assessed with CD31 immunohistochemistry. Matrix metalloproteinase 9 and interleukin 10 expressions were measured by Western blot, ELISA, and immunohistochemistry. Finally, we treated a macrophage cell line RAW264.7 with EtOH and measured changes in arginase I and iNOS expression. With EtOH exposure, macrophage density was positively correlated with MCP-1 expression. Macrophages infiltrated the tumor site, becoming tumor-associated macrophages that polarized to M2 phenotypes (ArgI(high) /iNOS(low) ) after EtOH treatment. Cancerous cells interacted with immune cells, especially M2 macrophages, and promoted tumor angiogenesis, progression, and invasiveness. RAW264.7 cells stimulated with EtOH expressed more arginase I and less iNOS than controls. These results agreed with the features of M2 phenotype macrophages (ArgI(high) /iNOS(low) ). Data show that EtOH induced M2 phenotype macrophages, suggesting that progression and metastasis of LLC may be mediated by recruitment of M2 macrophages, especially under the influence of EtOH.

Study on anti-tumor and anti-metastasis mechanism of alcohol extracts from Pharbitidis Semen against Lewis lung cancer

To observe the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer, and study its anti-tumor mechanism. In vitro, MTT assay and scratch assay were adopted to detect the effect of alcohol extracts from Pharbitidis Semen on the proliferation and metastasis of Lewis lung cancer cells. The cell autophagy was detected by the acridine orange staining. The gap-junction intercellular communication (GJIC) was investigated by the fluorescent yellow transfer. The expression of aquaporin 1 (AQP1) was analyzed by the Western blotting. In vivo, the subcutaneous implant model and the experimental pulmonary metastasis model of Lewis lung cancer in mice were established to evaluate the anti-tumor and anti-metastasis effects of alcohol extract from Pharbitidis Semen. The serum carcinoembryonic antigen (CEA) and beta2 microglobulin (beta2-MG) of mice bearing Lewis lung cancer were detected by the electrochemiluminesence immunoassay. The expressions of lung AQP1 and Connexin 43 (Cx43) were examined by the immunohistochemical method. In vitro, alcohol extracts from Pharbitidis Semen inhibited the cell proliferation in a dose-dependent matter, significantly prevented the cell migration, down-regulated AQP1 proteins of cells, promoted GJIC, and decreased the serum-free autophagy of tumor cells. In vivo, compared with untreated model mice, alcohol extracts from Pharbitidis Semen inhibited the tumor growth in a dose-dependent matter, prevented the tumor metastasis and prolonged the life span of mice bearing Lewis lung cancer, while decreasing serum CEA and beta2-MG of mice bearing Lewis lung cancer, enhancing the immumohistochemical staining intensity of Cx43 and weakening aquaporins AQP1 positive intensity. Alcohol extracts from Pharbitidis Semen could prevent the proliferation and metastasis in Lewis lung cancer cells. Its mechanism may be related to the promotion of GJIC and the down-regulation of AQP1.

Vaccaria segetalis extract can inhibit angiogenesis

Background: Study of antiangiogenic drugs is one of the cutting-edge fields in new antitumor drug development. However, system studies on Vaccaria segetalis extract as an inhibitor of tumor-induced neovascularization have not been published yet. In the current study, we performed a preliminary investigation of the antiangiogenic effect of Vaccaria segetalis extract on angiogenesis. Objective: We studied the inhibitory effect of Vaccaria segetalis extract on neovascularization. Methods: The effects of Vaccaria segetalis extract on in vitro proliferation, migration, and tube formation of human mammary endothelial cells (HMECs) were determined by 3 - (4,5) - dimethylthiahiazo (-z-y1) - 3, 5 -diphenytetrazoliumromide (MTT) assay and Matrigel plug assay. The antiangiogenic effect of Vaccaria segetalis extract was observed on the chick chorioallantoic-membrane (CAM) angiogenesis model. The CD31 expression on HMECs was detected by immunohistochemical staining. The therapeutic effect of Vaccaria segetalis extract on the metastasis of Lewis lung cancer was also observed in the mouse model. Results: The proliferation and migration of human mammary epithelial cells (HMECs) were inhibited significantly by Vaccaria segetalis extract in a dose-dependent manner (IC50 = 50 ?g/mL). Angiogenesis was also inhibited in the Matrigel-plug mouse model and the chick chorioallantoic-membrane model. The Vaccaria segetalis extract treatment reduced the expression of CD31 in HMECs and inhibited the growth and metastasis of Lewis lung carcinoma cells in the mouse model. Conclusion: The Vaccaria segetalis extract, which can obviously inhibit angiogenesis, could be developed as a promising new antiangiogenic drug. Keywords: Angiogenensis, CD31, endothelial cell, human mammary endothelial cells, Vaccaria segetalis

Chronic consumption of high‐fat diet stimulates tumor angiogenesis in the Lewis lung cancer allograft model

Epidemiological studies indicate that overweight and obesity are associated with increased risk of several cancers. In the present study, we determined whether a chronic consumption of high‐fat diet (HFD) increases tumor angiogenesis and metastasis of Lewis lung cancer in the C57BL/6N mice. Four‐week old, male mice were fed a purified control diet (CD, 10 kcal% fat) or HFD (60 kcal% fat) for 16 weeks, and then Lewis lung carcinoma cells were subcutaneously injected into the animals’ left flank. The primary tumor was resected 3 weeks later, and all animals were killed 21 days after the surgery. HFD feeding increased solid tumor growth and lung metastasis. Immunohistochemical staining of tumor tissues revealed that the expression of hypoxia‐inducible factor 1, vascular endothelial growth factor, and CD31 (an endothelial cell marker) was significantly increased in the HFD group compared to the CD group. HFD feeding significantly increased the blood levels of angiogenesis‐related proteins including leptin, monocyte chemoattractant protein‐1, angiogenin, angiopoietin‐1, angiopoietin‐3, chemokine ligand 16, plasminogen activator inhibitor‐1, stromal cell‐derived factor‐1, and endoglin. These results indicate that the prolonged consumption of HFD enhances the expression and secretion of angiogenesis‐related proteins.

P3-035: soluble vascular endothelial growth factor receptor 1(s VEGFR1) transducted by sendai virus using dendritic cells as vector inhibited HUVEC activity in vitro and growth and metastasis of Lewis lung cancer in vivo

P3-035: soluble vascular endothelial growth factor receptor 1(s VEGFR1) transducted by sendai virus using dendritic cells as vector inhibited HUVEC activity in vitro and growth and metastasis of Lewis lung cancer in vivo

Reduction of in vivo tumor growth by MMI-166, a selective matrix metalloproteinase inhibitor, through inhibition of tumor angiogenesis in squamous cell carcinoma cell lines of head and neck

Matrix metalloproteinases (MMPs) have been implicated in tumor invasion, metastasis, and angiogenesis. We have recently shown that MMI-166, a new orally active MMP inhibitor specific for MMP-2 and -9, suppressed experimental metastasis of Lewis lung cancer, C-H1 human colon cancer, and pancreatic cancer without affecting tumor growth in vitro. In the present study, we determined whether oral administration of MMI-166 reduces tumor growth not only in such tumors but also in squamous cell carcinoma of head and neck (SCCHN). MMI-166 inhibited both activity of MMP-2 and -9 without affecting steady state levels of their mRNAs in SCCHN. Interestingly, protein levels of MMP-2 and -9 from the cultures were drastically diminished by culturing with MMI-166. This was also observed in xenografts of MMI-166-administered mice. In addition, daily oral administration of MMI-166 (100 mg/kg) inhibited local tumor growth accompanied by the reduction of blood vessel density and Ki-67-positivity and increase in terminal deoxynucleotidyl transferase-mediated cUDP nick-end labeling (TUNEL)-positivity. These results suggested that orally administered MMI-166 reduced in vivo tumor growth of SCCHN through inhibition of angiogenesis and induction of apoptosis accompanied by the reduction of MMP productions and activities. Therefore, MMI-166 seems to be useful for tumor dormancy therapy of SCCHN.

Effects of superoxide dismutase on some biological characteristics of lung cancer cellsIn vivo andIn vitro

The present study observed the effects of superoxide dismutase (SOD) and its inhibitor, diethyldithiocarbamate (DDC), on the metastasis of Lewis Lung cancer and some biological characteristics of A549 lung cancer cell line. It was found that SOD and DDC inhibited significantly the metastasis of Lewis lung cancer in C57 BL mice, which the effect of DDC was more significant than that of SOD, and decreased the proliferation of A549 lung cancer cell and its transplantation rate in nude mice.