scholarly journals S-Allylcysteine inhibits tumour progression and the epithelial–mesenchymal transition in a mouse xenograft model of oral cancer

2011 ◽  
Vol 108 (1) ◽  
pp. 28-38 ◽  
Author(s):  
Man-Hui Pai ◽  
Yueh-Hsiung Kuo ◽  
En-Pei Isabel Chiang ◽  
Feng-Yao Tang
Keyword(s):  
Oral Cancer ◽  
Tumour Growth ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Progression ◽  
D1 Protein ◽  
Xenograft Model ◽  
Mesenchymal Transition ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Oral cancer is prevalent worldwide. Studies have indicated that an increase in the osteopontin (OPN) plasma level is correlated with the progression of oral cancer. Our previous report showed that the aqueous garlic extract S-allylcysteine (SAC) inhibited the epithelial–mesenchymal transition (EMT) of human oral cancer CAL-27 cells in vitro. Therefore, the present study investigated whether SAC consumption would help prevent tumour growth and progression, including the EMT, in a mouse xenograft model of oral cancer. The results demonstrated that SAC dose-dependently inhibited the growth of oral cancer in tumour-bearing mice. The histopathological and immunohistochemical staining results indicated that SAC was able to effectively suppress the tumour growth and progression of oral cancer in vivo. The chemopreventive effect of SAC was associated with the suppression of carcinogenesis factors such as N-methylpurine DNA glycosylase and OPN. SAC significantly suppressed the phosphorylation of Akt, mammalian target of rapamycin, inhibitor of κBα and extracellular signal-regulated kinase 1/2 in tumour tissues. The results demonstrated that the SAC-mediated suppression of cyclin D1 protein was associated with an augmented expression of the cell-cycle inhibitor p16Ink4. Furthermore, SAC inhibited the expression of cyclo-oxygenase-2, vimentin and NF-κB p65 (RelA). These results show that SAC has potential as an agent against tumour growth and the progression of oral cancer in a mouse xenograft model.

scholarly journals Hypoxia downregulated miR-4521 suppresses gastric carcinoma progression through regulation of IGF2 and FOXM1

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Shan Xing ◽  
Zhi Tian ◽  
Wenying Zheng ◽  
Wenjuan Yang ◽  
Nan Du ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Clinical Stage ◽  
Xenograft Model ◽  
Regulatory Mechanisms ◽  
Mesenchymal Transition ◽  
Mouse Xenograft Model

Abstract Background MicroRNAs (miRNAs) show considerable promise as therapeutic agents to improve tumor treatment, as they have been revealed as crucial modulators in tumor progression. However, our understanding of their roles in gastric carcinoma (GC) metastasis is limited. Here, we aimed to identify novel miRNAs involved in GC metastasis and explored their regulatory mechanisms and therapeutic significance in GC. Methods The microRNA expression profiles of GC tumors at different stages and at different metastasis statuses were compared respectively using the stomach adenocarcinoma (STAD) miRNASeq dataset in TCGA. Using the above method, miR-4521 was picked out for further study. miR-4521 expression in GC tissues was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH). Highly and lowly invasive cell sublines were established using a repetitive transwell assay. Gain-of-function and loss-of-function analyses were performed to investigate the functions of miR-4521 and its upstream and downstream regulatory mechanisms in vitro and in vivo. Moreover, we investigated the therapeutic role of miR-4521 in a mouse xenograft model. Results In this study, we found that miR-4521 expression was downregulated in GC tissues compared with adjacent normal tissues and that its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. Functional experiments revealed that miR-4521 inhibited GC cell invasion and metastasis in vitro and in vivo. Further studies showed that hypoxia repressed miR-4521 expression via inducing ETS1 and miR-4521 mitigated hypoxia-mediated metastasis, while miR-4521 inactivated the AKT/GSK3β/Snai1 pathway by targeting IGF2 and FOXM1, thereby inhibiting the epithelial-mesenchymal transition (EMT) process and metastasis. In addition, we demonstrated that therapeutic delivery of synthetic miR-4521 suppressed gastric carcinoma progression in vivo. Conclusions Our results suggest an important role for miR-4521 in regulating GC metastasis and hypoxic response of tumor cells as well as the therapeutic significance of this miRNA in GC.

scholarly journals Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 20 ◽  
Author(s):  
Li-Fang Chou ◽  
Chi-Yuan Chen ◽  
Wan-Hua Yang ◽  
Chin-Chuan Chen ◽  
Junn-Liang Chang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cell Function ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Loss Of Function ◽  
Chinese Medicinal Herb ◽  
Mesenchymal Transition ◽  
Mouse Xenograft Model

Daphne genkwa, a Chinese medicinal herb, is used frequently in Southeast Asian countries to treat diseases; the flavonoid hydroxygenkwanin (HGK) is extracted from its flower buds. The bioactivity of HGK, particularly as an anti-liver cancer agent, has not been explored. In this study, human hepatocellular carcinoma (HCC) cell lines and an animal xenograft model were employed to investigate both the activity of HGK against liver cancer and its cellular signaling mechanisms. HCC cells treated with HGK were subjected to cell function assays. Whole transcriptome sequencing was used to identify genes whose expression was influenced by HGK, and the flavonoid’s cancer suppression mechanisms were further investigated through gain- and loss-of-function assays. Finally, in vitro findings were tested in a mouse xenograft model. The data showed that HGK induced the expression of the microRNA miR-320a, which in turn inhibited the expression of the transcription factor ‘forkhead box protein M1’ (FOXM1) and downstream FOXM1-regulated proteins related to epithelial–mesenchymal transition, thereby leading to the suppression of liver cancer cell growth and invasion. Significant inhibition of tumor growth was also observed in HGK-treated mice. Hence, the present study demonstrated the activity of HGK against liver cancer and validated its potential use as a therapeutic agent.

scholarly journals Inhibitory role of ATF3 in gastric cancer progression through regulating cell EMT and stemness

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuanqian Huang ◽  
Renli Chen ◽  
Fangjing Zheng ◽  
Yirong Tang ◽  
Xiukang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Colony Formation ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Mesenchymal Transition ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Abstract Background Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer related mortality worldwide. The 5-year survival rate is rather low owing to advanced unresectable and distant metastasis. The EMT has been widely implicated in the stemness, metastatic dormancy, and chemoresistance of different solid tumors. Given the fact that activating transcription factor-3 (ATF3) is a member of the ATF/CREB family of transcription factors and its role in regulation of GC recurrence and metastasis remain poorly understood, the aim of the present study was to investigate its potential impact in epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) properties and GC aggression. Methods To elucidate the potential role of ATF3 in gastric cancer, we utilized SGC-7901 and MGC-803 gastric cancer cell lines as research models and constructed stable cell lines overexpressing ATF3. We conducted a series of assays including cell proliferation, colony formation, cell migration, tumorsphere formation, and invasion to investigate the functional roles of ATF3 in stemness of gastric cancer. The possible effect of ATF3 on epithelial–mesenchymal transition (EMT) was assessed through flow cytometry and qRT-PCR. In vivo functional effect of upregulation of ATF3 on tumor growth was examined in a mouse xenograft model. Results We found that overexpression of ATF3 inhibited cell proliferation, colony formation, cell migration and invasion. In addition, up-regulation of ATF3 attenuated tumorsphere formation, cell stemness, and potentially decreased expression of EMT markers. Moreover, ATF3 overexpression inhibited tumorigenesis in mouse xenograft model. Conclusion Our data suggest a suppressive role of ATF3 in gastric cancer development. Our findings will provide a potential therapeutic strategy and novel drug target for gastric cancer.

scholarly journals Osteopontin Regulates Epithelial Mesenchymal Transition-Associated Growth of Hepatocellular Cancer in a Mouse Xenograft Model

2012 ◽  
Vol 255 (2) ◽  
pp. 319-325 ◽  
Author(s):  
Syamal D. Bhattacharya ◽  
Zhiyong Mi ◽  
Victoria M. Kim ◽  
Hongtao Guo ◽  
Lindsay J. Talbot ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Hepatocellular Cancer ◽  
Mesenchymal Transition ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

scholarly journals Oncogenic lncRNA ZNF561-AS1 is essential for colorectal cancer proliferation and survival through regulation of miR-26a-3p/miR-128-5p-SRSF6 axis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zizhen Si ◽  
Lei Yu ◽  
Haoyu Jing ◽  
Lun Wu ◽  
Xidi Wang
Keyword(s):  
Colorectal Cancer ◽  
Rna Binding ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Cancer Proliferation ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model

Abstract Background Long non-coding RNAs (lncRNA) are reported to influence colorectal cancer (CRC) progression. Currently, the functions of the lncRNA ZNF561 antisense RNA 1 (ZNF561-AS1) in CRC are unknown. Methods ZNF561-AS1 and SRSF6 expression in CRC patient samples and CRC cell lines was evaluated through TCGA database analysis, western blot along with real-time PCR. SRSF6 expression in CRC cells was also examined upon ZNF561-AS1 depletion or overexpression. Interaction between miR-26a-3p, miR-128-5p, ZNF561-AS1, and SRSF6 was examined by dual luciferase reporter assay, as well as RNA binding protein immunoprecipitation (RIP) assay. Small interfering RNA (siRNA) mediated knockdown experiments were performed to assess the role of ZNF561-AS1 and SRSF6 in the proliferative actives and apoptosis rate of CRC cells. A mouse xenograft model was employed to assess tumor growth upon ZNF561-AS1 knockdown and SRSF6 rescue. Results We find that ZNF561-AS1 and SRSF6 were upregulated in CRC patient tissues. ZNF561-AS1 expression was reduced in tissues from treated CRC patients but upregulated in CRC tissues from relapsed patients. SRSF6 expression was suppressed and enhanced by ZNF561-AS1 depletion and overexpression, respectively. Mechanistically, ZNF561-AS1 regulated SRSF6 expression by sponging miR-26a-3p and miR-128-5p. ZNF561-AS1-miR-26a-3p/miR-128-5p-SRSF6 axis was required for CRC proliferation and survival. ZNF561-AS1 knockdown suppressed CRC cell proliferation and triggered apoptosis. ZNF561-AS1 depletion suppressed the growth of tumors in a model of a nude mouse xenograft. Similar observations were made upon SRSF6 depletion. SRSF6 overexpression reversed the inhibitory activities of ZNF561-AS1 in vivo, as well as in vitro. Conclusion In summary, we find that ZNF561-AS1 promotes CRC progression via the miR-26a-3p/miR-128-5p-SRSF6 axis. This study reveals new perspectives into the role of ZNF561-AS1 in CRC.

scholarly journals RBFOX3 Regulates the Chemosensitivity of Cancer Cells to 5-Fluorouracil via the PI3K/AKT, EMT and Cytochrome-C/Caspase Pathways

2018 ◽  
Vol 46 (4) ◽  
pp. 1365-1380 ◽  
Author(s):  
Tianze Liu ◽  
Xiaojun Wu ◽  
Yizhuo Li ◽  
Wenjing Lu ◽  
Fufu Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cytochrome C ◽  
Rna Binding ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model ◽  
Hcc Cells

Background/Aims: RBFOX3, an RNA-binding fox protein, plays an important role in the differentiation of neuronal development, but its role in the chemosensitivity of hepatocellular carcinoma (HCC) to 5-FU is unknown. Methods: In this study, we examined the biological functions of RBFOX3 and its effect on the chemosensitivity of HCC cells to 5-FU in vitro and in a mouse xenograft model. Results: RBFOX3 was found to have elevated expression in HCC cell lines and tissue samples, and its knockdown inhibited HCC cell proliferation. Moreover, knockdown of RBFOX3 improved the inhibitory effect of 5-fluorouracil (5-FU) on cell proliferation, migration and invasion, and enhanced the apoptosis induced by 5-FU. However, overexpression of RBFOX3 reduced the inhibitory effect of 5-fluorouracil (5-FU) on cell proliferation, migration and invasion, and decreased the apoptosis induced by 5-FU. We further elucidated that RBFOX3 knockdown synergized with 5-FU to inhibit the growth and invasion of HCC cells through PI3K/AKT and epithelial-mesenchymal transition (EMT) signaling, and promote apoptosis by activating the cytochrome-c/caspase signaling pathway. Finally, we validated that RBFOX3 regulated 5-FU-mediated cytotoxicity in HCC in mouse xenograft models. Conclusions: The findings from this study indicate that RBFOX3 regulates the chemosensitivity of HCC to 5-FU in vitro and in vivo. Therefore, targeting RBFOX3 may improve the inhibition of HCC growth and progression by 5-FU, and provide a novel potential therapeutic strategy for HCC.

scholarly journals Elevated Expression Levels of PC3-Secreted Microprotein (PSMP) in Prostate Cancer Associated With Increased Xenograft Growth and Modification of Immune-Related Microenvironment

2019 ◽  
Vol 9 ◽  
Author(s):  
Xiaolei Pei ◽  
Danfeng Zheng ◽  
Shaoping She ◽  
Zhiwei Fang ◽  
Shiying Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Neutralizing Antibodies ◽  
Epithelial Mesenchymal Transition ◽  
Macrophage Polarization ◽  
Xenograft Model ◽  
Metastatic Progression ◽  
Male Mortality ◽  
Mesenchymal Transition ◽  
Monocyte Migration

Prostate cancer (PCa), especially metastatic PCa, is one of the main cancer types accounting for male mortality worldwide. Over decades, researchers have tried to search for effective curative methods for PCa, but many attempts have failed. The therapeutic failure of PCa is usually due to off-target or side effects; thus, finding a key molecule that could prevent PCa metastatic progression has become the most important goal for curing aggressive PCa. In this study, we collected hundreds of PCa tissues and serum and urine samples from patients to verify the upregulated expression of PC3-secreted microprotein (PSMP) in PCa tumor tissues with high Gleason scores. According to biopsy results, PSMP expression was found related to extraprostatic extension (EPE), contributing to PCa metastasis. Mechanistically, recombinant PSMP protein could promote the proliferation both in vitro and in vivo, and rhPSMP could promote epithelial–mesenchymal transition (EMT) of PC3 in vitro. Additionally, PSMP could also influence cytokine production in the xenograft model and monocyte migration and macrophage polarization in vitro. Our most important finding was that neutralizing antibodies against PSMP could suppress xenograft PC3 growth and promote the survival of PC3 metastatic mice model, providing an effective option to cure human PCa.

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