scholarly journals Metformin Inhibited Growth, Invasion and Metastasis of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo

2018 ◽  
Vol 51 (3) ◽  
pp. 1276-1286 ◽  
Author(s):  
Feng Liang ◽  
Yu-Gang Wang ◽  
Changcheng Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Plasma Glucose Level ◽  
Caspase 3 ◽  
Time Dependent ◽  
Dependent Manner ◽  
Metformin Treatment ◽  
Invasion And Migration ◽  
And Migration

Background/Aims: This study aimed at investigating the effects of metformin on the growth and metastasis of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Methods: Two human ESCC cell lines EC9706 and Eca109 were selected and challenged with metformin in this study. Western blot assay was performed to detect th level of Bcl-2, Bax and Caspase-3. Scratch wound assay, transwell assay and Millicell invasion assay were used to assay the invasion and migration of EC9706 and Eca109 cells. Nude mice tumor models were used to assay the growth and lung metastasis of ESCC cells after metformin treatment. The plasma glucose level was also assayed. Results: We found that metformin significantly inhibited proliferation and induced apoptosis of both ESCC cell lines in a dose- and time-dependent manner, and the expression of Bcl-2 was down-regulated and Bax and Caspase-3 were up-regulated. Metformin significantly inhibited the invasion and migration of EC9706 and Eca109 cells (p < 0.05). mRNA and protein levels of MMP-2 and MMP-9 decreased significantly upon treatment with metformin of 10mM for 12, 24 and 48h in a time-dependent manner (p < 0.05). In line with in vitro results, in vivo experiments demonstrated that metformin inhibited tumorigenicity, inhibited lung metastasis and down-regulated the expression of MMP-2 and MMP-9. Moreover, we showed that metformin treatment did not cause significant alteration in liver and renal functions and plasma glucose level. Conclusion: Our study for the first time demonstrated the anti-invasive and anti-metastatic effects of metformin on human ESCC cells both in vitro and in vivo, which might be associated with the down-regulation of MMP-2 and MMP-9. As a whole, our results indicate the potential of metformin to be developed as a chemotherapeutic agent for patients with ESCC and might stimulate future studies on this area.

scholarly journals HDAC2 enhances esophageal squamous cell carcinoma development through down-regulating microRNA-503-5p and promoting CXCL10

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jindong Li ◽  
Chengyan Jin ◽  
Lihua Sun ◽  
Bin Wang ◽  
Peiyan Hua ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Invasion And Migration ◽  
Histone Deacetylase 2 ◽  
Mucosal Tissues ◽  
And Migration

Abstract Objective Although esophageal squamous cell carcinoma (ESCC)-oriented mechanism has been widely explored, the integrated action of histone deacetylase 2 (HDAC2), microRNA (miR)-503-5p and C-X-C motif chemokine 10 (CXCL10) in ESCC has not been thoroughly explored. Thus, we performed the research to study the role of HDAC2/miR-503-5p/CXCL10 axis in ESCC. Methods ESCC tissues and mucosal tissues (5 cm from cancer tissues) were collected, in which HDAC2, miR-503-5p and CXCL10 expression levels were tested. The mechanism of HDAC2, miR-503-5p and CXCL10 was interpreted. The viability, colony formation ability, apoptosis, invasion and migration abilities of ESCC cells were tested after HDAC2, miR-503-5p or CXCL10 expression was altered. Tumorigenesis in mice was observed to further verify the in vitro effects of HDAC2 and miR-503-5p. Results HDAC2 and CXCL10 were up-regulated while miR-503-5p was down-regulated in ESCC. HDAC2 bound to miR-503-5p and miR-503-5p targeted CXCL10. Silencing HDAC2 or restoring miR-503-5p depressed viability, colony-forming, invasion and migration abilities and enhanced apoptosis of ESCC cells in vitro, as well as suppressed ESCC tumorigenesis in vivo. Inhibition of miR-503-5p or elevation of CXCL10 negated HDAC2 knockout-induced effects on ESCC cells. Conclusion This work elucidates that HDAC2 knockdown retards the process of ESCC by elevating miR-503-5p and inhibiting CXCL10 expression, which may provide a guidance for ESCC management.

scholarly journals Knockdown of RhoC Inhibits Oral Squamous Cell Carcinoma Cell Invasion and Metastasis via Regulation of HMGA2

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Feng Gao ◽  
Panpan Yin ◽  
Yanlin Wu ◽  
Jinlin Wen ◽  
Ying Su ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Invasion And Metastasis ◽  
Invasion And Migration ◽  
Node Metastasis ◽  
Tumor Tissues ◽  
And Migration ◽  
Rhoc Expression

Ras homolog family member C (RhoC) is an important component of intracellular signal transduction and its overexpression has been reported to be involved in regulating tumor proliferation, invasion, and metastasis in various malignant tumors. However, its role and underlying mechanism in oral squamous cell carcinoma (OSCC) still remain obscure. In our study, RhoC expression, its relation with clinical stages, and survival rate in OSCC were analyzed using datasets from The Cancer Genome Atlas (TCGA). Next, a RhoC knockdown cell model was established in vitro, and the effects of RhoC knockdown in OSCC cells were detected by the MTT assay, colony formation assay, transwell invasion assay, scratch assay, and F-actin phalloidin staining. An in vivo tongue-xenografted nude mouse model was established to measure the effects of knockdown of RhoC on tumor cell growth and lymph node metastasis. A mechanism study was conducted by real-time PCR and immunocytochemistry. The results of TCGA analysis showed that RhoC was overexpressed in OSCC tumor tissues. In vitro assays indicated that knockdown of RhoC did not have much effect on OSCC cell growth but significantly suppressed cell colony formation, invasion, and migration abilities, and F-actin polymerization was also reduced. The tongue-xenografted in vivo model demonstrated that knockdown of RhoC suppressed OSCC cell growth and inhibited metastasis to the superficial cervical lymph nodes. Further mechanism studies showed that knockdown of RhoC downregulated HMGA2 expression, and HMGA2 expression was highly correlated with RhoC expression in OSCC tumor tissues via the analysis of TCGA datasets. Overall, our study showed that knockdown of RhoC inhibited OSCC cells invasion and migration in vitro and OSCC cell growth and lymph node metastasis in vivo. Moreover, the potential mechanisms involved in these activities may be related to the regulation of HMGA2 expression. The RhoC gene could serve as a promising therapeutic target for OSCCs in the future.

MTA1 promotes tumorigenesis and development of esophageal squamous cell carcinoma via activating the MEK/ERK/p90RSK signaling pathway

2019 ◽  
Vol 41 (9) ◽  
pp. 1263-1272 ◽  
Author(s):  
Peng Nan ◽  
Ting Wang ◽  
Chunxiao Li ◽  
Hui Li ◽  
Jinsong Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Colony Formation ◽  
Cancer Proliferation ◽  
Invasion And Migration ◽  
And Migration

Abstract Metastasis-associated protein 1 (MTA1) is upregulated in multiple malignancies and promotes cancer proliferation and metastasis, but whether and how MTA1 promotes esophageal squamous cell carcinoma (ESCC) tumorigenesis remain unanswered. Here, we established an ESCC model in MTA1 transgenic mice induced by the chemical carcinogen 4-nitroquinoline 1-oxide (4-NQO) and found that MTA1 promotes ESCC tumorigenesis in mice. MTA1 overexpression was observed in ESCC cells and clinical ESCC samples. Overexpressed MTA1 increased colony formation and the invasiveness and migration of ESCC cells, whereas knock down of MTA1 in ESCC cells significantly decreased colony formation, invasion and migration in vitro and inhibited the growth of xenograft tumors in vivo. RNA sequencing (RNA-seq) analysis combined with western blot assays revealed that MTA1 promotes carcinogenesis by enhancing MEK/ERK/p90RSK signaling. The phosphorylation of MEK, ERK and their downstream target p90RSK was significantly decreased after MTA1 knockdown in ESCC cells and was increased in MTA1-overexpressing cells. Moreover, colony formation, invasion and migration potential were dramatically suppressed when cells overexpressing MTA1 were treated with MEK (PD0325901) or ERK (SCH772948) inhibitors. In conclusion, MTA1 plays a pivotal oncogenic role in ESCC tumorigenesis and development through activating the MEK/ERK/p90RSK pathway.

scholarly journals Erratum

2021 ◽  
Vol 28 (6) ◽  
pp. 681-682
Author(s):  
Juan Gu ◽  
Chang-fu Cui ◽  
Li Yang ◽  
Ling Wang ◽  
Xue-hua Jiang
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Mrna Level ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Invasion And Migration ◽  
Downstream Target ◽  
And Migration

Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant mechanism of emodin on the invasion and migration of CC in vitro and in vivo. In our study, we found that emodin inhibited the invasion and migration abilities of RKO cells and decreased the expression of matrix metalloproteinase-7 (MMP-7), MMP-9, and vascular endothelial growth factor (VEGF) in a dose-dependent manner. Further research suggested that emodin inhibited EMT by increasing the mRNA level of E-cadherin and decreasing the expression of N-cadherin, Snail, and -catenin. Emodin also significantly inhibited the activation of the Wnt/-catenin signaling pathway by downregulating the expression of related downstream target genes, including TCF4, cyclin D1, and c-Myc. A Wnt/-catenin signaling pathway agonist abolished the effect of emodin on EMT and cell mobility, suggesting that emodin exerted its regulating role through the Wnt/-catenin pathway. The CC xenograft model was established to study the antitumor efficiency of emodin in vivo. The in vivo study further demonstrated that emodin (40 mg/kg) suppressed tumor growth by inhibiting EMT via the Wnt/-catenin signaling pathway in vivo. Taken together, we suggest that emodin inhibits the invasion and migration of CC cells in vitro and in vivo by blocking EMT, which is related with the inhibition of the Wnt/-catenin signaling pathway.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

scholarly journals Circular METRN RNA hsa_circ_0037251 Promotes Glioma Progression by Sponging miR-1229-3p and Regulating mTOR Expression

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Qinchen Cao ◽  
Yonggang Shi ◽  
Xinxin Wang ◽  
Jing Yang ◽  
Yin Mi ◽  
...  
Keyword(s):  
Glioma Cell ◽  
High Expression ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
Cellular Processes ◽  
Cell Progression ◽  
And Migration ◽  
Glioma Progression

AbstractCircular RNAs (circRNAs) are a newly identifed non-coding RNA in many cellular processes and tumours. This study aimed to investigate the role of hsa_circ_0037251, one circRNA generated from several exons of the gene termed METRN, in glioma progression. Through in vitro experiments, we discovered that high expression of hsa_circ_0037251 was related to low expression of the microRNA miR-1229-3p and high expression of mTOR. The over-expressed hsa_circ_0037251 promoted cell proliferation, invasion and migration in glioma, while knockdown of hsa_circ_00037251 promoted cell apoptosis and induced G1 phase arrest. Then, hsa_circ_0037251 was observed to directly sponge miR-1229-3p, and mTOR was identified as a direct target of miR-1229-3p. In addition, knockdown of hsa_circ_0037251 up-regulated the expression of miR-1229-3p and inhibited the expression of mTOR. And overexpression of miR-1229-3p or low-expressed mTOR inhibited the glioma cell progression. Furthermore, transfection with mTOR overexpression vectors can restore the abilities of glioma cell progression even if hsa_circ_00037251 was knocked down using siRNAs. In vivo experiments revealed that hsa_circ_00037251 promoted the growth of xenografted tumours and shortened the survival period. These results indicated that hsa_circ_0037251 may act as a tumour promoter by a hsa_circ_0037251/miR-1229-3p/mTOR axis, and these potential biomarkers may be therapeutic targets for glioma.

scholarly journals β-carotene Suppresses Colon Cancer by Regulating M2 Macrophages and Tumor-associated Fibroblasts in Vitro and in Vivo (P02-015-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yerin Kim ◽  
Na Youn Lee ◽  
Yoo Sun Kim ◽  
Yuri Kim
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Invasion And Migration ◽  
And Migration ◽  
Emt Markers ◽  
Β Carotene

Abstract Objectives Tumor-associated macrophages (TAMs) and tumor-associated fibroblasts (TAFs) are consisted of tumor microenvironment (TME), which are involved in cancer progression and metastasis. Interactions within TME induce M2 macrophage phenotype, TAMs, and activate TAFs. β-carotene (BC) is a well-known antioxidant and showed protective effects on several diseases, including cancers. The object of this study is to investigate the anti-colorectal cancer (CRC) effects of BC by controlling macrophage polarization and fibroblast activation. Methods TAMs were induced by treating with phorbol-12-myristate-13-acetate (PMA) and interleukin-4 (IL-4) in U937 cells and TAFs were induced by treating with transforming growth factor-β1 (TGF-β1) in CCD-18Co cells. To understand the effect of TME on cancer cells, HCT116 colon cancer cells were co-cultured with TAM or TAF conditioned media. The effects of BC on the expressions of cancer stem cells (CSCs) markers, epithelial-mesenchymal transition (EMT) markers along with invasion and migration were investigated. To confirm these results, the azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colitis-associated CRC mice model was used. Results BC decreased M2 macrophage polarization with activating IL-6/STAT3 signaling pathways and suppressed the expressions of fibroblast activation markers and EMT markers. In addition, BC inhibited the expressions of TME-induced CSCs markers and EMT and suppressed cell invasion and migration. Furthermore, BC supplementation suppressed tumorigenesis and the expressions of M2 macrophage-associated markers, including CD206, Arg1, and Ym-1 as well as CSCs markers in vivo. Conclusions BC suppressed CRC by regulating TAMs and TAFs in vitro and in vivo, which indicated the potential therapeutic effects of BC on inflammatory diseases. Funding Sources This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education and Brain Korea 21 Plus.

SM22α inhibits lamellipodium formation and migration via Ras-Arp2/3 signaling in synthetic VSMCs

2016 ◽  
Vol 311 (5) ◽  
pp. C758-C767 ◽  
Author(s):  
Pin Lv ◽  
Fan Zhang ◽  
Ya-Juan Yin ◽  
Yu-Can Wang ◽  
Min Gao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Lesion ◽  
Flavonoid Compound ◽  
Cell Cortex ◽  
Dependent Manner ◽  
Nucleotide Exchange ◽  
Migration Activity ◽  
And Migration

We previously demonstrated that smooth muscle (SM) 22α promotes the migration activity in contractile vascular smooth muscle cells (VSMCs). Based on the varied functions exhibited by SM22α in different VSMC phenotypes, we investigated the effect of SM22α on VSMC migration under pathological conditions. The results demonstrated that SM22α overexpression in synthetic VSMCs inhibited platelet-derived growth factor (PDGF)-BB-induced cell lamellipodium formation and migration, which was different from its action in contractile cells. The results indicated two distinct mechanisms underlying inhibition of lamellipodium formation by SM22α, increased actin dynamic stability and decreased Ras activity via interference with interactions between Ras and guanine nucleotide exchange factor. The former inhibited actin cytoskeleton rearrangement in the cell cortex, while the latter significantly disrupted actin nucleation activation of the Arp2/3 complex. Baicalin, a herb-derived flavonoid compound, inhibited VSMC migration via upregulation of SM22α expression in vitro and in vivo. These data suggest that SM22α regulates lamellipodium formation and cell migration in a phenotype-dependent manner in VSMCs, which may be a new therapeutic target for vascular lesion formation.

scholarly journals Suppression of long noncoding RNA MALAT1 inhibits the development of uveal melanoma via microRNA-608-mediated inhibition of HOXC4

2020 ◽  
Vol 318 (5) ◽  
pp. C903-C912 ◽  
Author(s):  
Shuai Wu ◽  
Han Chen ◽  
Ling Zuo ◽  
Hai Jiang ◽  
Hongtao Yan
Keyword(s):  
Cell Cycle ◽  
Uveal Melanoma ◽  
Noncoding Rna ◽  
Cell Cycle Progression ◽  
Melanoma Cells ◽  
Cell Cycle Distribution ◽  
Invasion And Migration ◽  
And Migration

This study explored the effects of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the development of uveal melanoma. Moreover, the role of the MALAT1/microRNA-608 (miR-608)/homeobox C4 (HOXC4) axis was assessed by evaluating the proliferation, invasion, and migration, as well as the cell cycle distribution of uveal melanoma in vitro after knocking down MALAT1 or HOXC4 and/or overexpression of miR-608 in uveal melanoma cells (MUM-2B and C918). Moreover, the effects of the MALAT1/miR-608/HOXC4 axis in uveal melanoma in vivo were further evaluated by injecting the C918 cells into the NOD/SCID mice. HOXC4 was found to be a gene upregulated in uveal melanoma, while knockdown of its expression resulted in suppression of uveal melanoma cell migration, proliferation, and invasion, as well as cell cycle progression. In addition, the upregulation of miR-608 reduced the expression of HOXC4 in the uveal melanoma cells, which was rescued by overexpression of MALAT1. Hence, MALAT1 could upregulate the HOXC4 by binding to miR-608. The suppressed progression of uveal melanoma in vitro by miR-608 was rescued by overexpression of MALAT1. Additionally, in vivo assays demonstrated that downregulation of MALAT1 could suppress tumor growth through downregulation of HOXC4 expression via increasing miR-608 in uveal melanoma. In summary, MALAT1 downregulation functions to restrain the development of uveal melanoma via miR-608-mediated inhibition of HOXC4.

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