scholarly journals Zinc oxide nanosphere for hydrogen sulfide scavenging and ferroptosis of colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiang Pan ◽  
Yuchen Qi ◽  
Zhen Du ◽  
Jian He ◽  
Sheng Yao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Zinc Oxide ◽  
Hydrogen Sulfide ◽  
Cancer Model ◽  
Tumor Tissues ◽  
Breast Cancer Model ◽  
Colorectal Cancer Cells ◽  
Low Toxicity ◽  
4T1 Breast Cancer ◽  
Common Malignancy

Abstract Background Colorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy. Methods Here, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer. Results Owing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model. Conclusions We anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise. Graphic abstract

Hypoxia Facilitates the Proliferation of Colorectal Cancer Cells by Inducing Cancer-associated Fibroblast-derived IL6.

2021 ◽  
Author(s):  
Ying Xu ◽  
Rong Kuai ◽  
Yimin Chu ◽  
Lu Zhou ◽  
Hai-qin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Cancer Associated Fibroblast ◽  
Stat3 Signaling ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
Development Methods ◽  
Multiplex Cytokine ◽  
Common Malignancy

Abstract Background: Colorectal cancer (CRC) is most common malignancy worldwide, and its underlying molecular mechanisms remain largely unexplored. Accumulating evidences indicate Cancer-Associated Fibroblasts (CAFs), abundant stromal cell population in the tumor microenvironment, play a key role in tumor development. Methods: We have successfully isolated CAFs and paired normal fibroblasts (NFs) from colorectal cancer tissues (n=10). By using multiplex cytokine profiling assay, we have identified IL-6 as a major cytokine released by CAFs. Coculturing of CAFs with CRC cell lines HCT116 or SW480 increase IL-6 release, and the secretion by CAFs can be further enhanced under hypoxia. By using CCK-8 assay, we have found HCT116 or SW480 cells treated with culture medium from CAFs, IL-6 or hypoxia showed a significant cell growth compared to control cells (P<0.01). Results: Mechanistically, we have found hypoxia can enhanced effect of IL-6/STAT3 signaling on CRC cells, in part, throughHIF-1a targets PKM2. Conclusions: In conclusion, our data clearly proposes the interconnected mechanisms for a constitutive activation of STAT3 signalby CAFs-derived IL-6 under hypoxia in colorectal cancer. The pharmacological inhibition of STAT3, PKM2 or HIF-1α can significantly reduce oncogenic effect of IL-6, providing a potential therapeutic target for CRC patients.Trail registration: Not applicable

scholarly journals MicroRNA-490-3p inhibits migration and chemoresistance of colorectal cancer cells via targeting TNKS2

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jing Li ◽  
Rubing Mo ◽  
Linmei Zheng
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Target Genes ◽  
Chemotherapy Resistance ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Colorectal Cancer Cells ◽  
And Migration ◽  
Common Malignancy

Abstract Objective Colorectal cancer is one of the most common malignancy in the world. The oncogenesis of colorectal cancer is still not fully elucidated. It was reported that microRNA-490-3p (miR-490-3p) was closely related to the regulation of cancers. However, if miR-490-3p could also affect colorectal cancer and the specific mechanism remains unclear. Methods qRT-PCR was conducted to examine the expression of miR-490-3p. DIANA, miRDB, and TargetScan databases were used to identify target genes. LOVO and SW480 cells were transfected by miR-490-3p mimics and inhibitors. Transwell assay was used to measure cell invasion and migration. Cisplatin and fluorouracil were administered to investigate chemotherapy resistance. Western blot was used to measure TNKS2 protein expression. Binding sites were verified using the double luciferase assay. Results miR-490-3p expression was low in the colorectal cancer cells. The level of miR-490-3p was negatively correlated with cell migration and invasion of cancer cells. miR-490-3p could bind to TNKS2 mRNA 3′UTR directly. miR-490-3p can suppress cell viability and resistance to chemotherapy in colorectal cancer cells through targeting TNKS2. Conclusions miR-490-3p could affect colorectal cancer by targeting TNKS2. This study may provide a potential therapeutic target for colorectal cancer.

scholarly journals Theranostic probe for simultaneous in vivo photoacoustic imaging and confined photothermolysis by pulsed laser at 1064 nm in 4T1 breast cancer model

Nanoscale ◽  
2014 ◽  
Vol 6 (24) ◽  
pp. 15228-15235 ◽  
Author(s):  
Min Zhou ◽  
Geng Ku ◽  
Laura Pageon ◽  
Chun Li
Keyword(s):  
Breast Cancer ◽  
Photoacoustic Imaging ◽  
Pulsed Laser ◽  
Tumor Ablation ◽  
Cancer Model ◽  
Single Compartment ◽  
Breast Cancer Model ◽  
Nanoparticle System ◽  
4T1 Breast Cancer

A single-compartment nanoparticle system mediates dual photoacoustic imaging and confined thermolysis for tumor ablation.

scholarly journals Activation of CXCL12/CXCR4 renders colorectal cancer cells less sensitive to radiotherapy via up-regulating the expression of survivin

2016 ◽  
Vol 242 (4) ◽  
pp. 429-435 ◽  
Author(s):  
Dawei Wang ◽  
Chengbin Jiao ◽  
Yanli Zhu ◽  
Deshen Liang ◽  
Ming Zao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Underlying Mechanism ◽  
Caspase 9 ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis ◽  
Common Malignancy ◽  
Cxcr4 Axis

Colorectal cancer is the most common malignancy of the gastrointestinal tract. Surgical treatment combined with radiotherapy is the main treatment course for colorectal cancer; nevertheless, radio-resistance is commonly encountered during the treatment course and seriously influences the therapeutic efficacy. We tested the hypothesis that the CXCL12/CXCR4 axis is closely related to radiotherapy sensitivity in colorectal cancer cells. Here, we found that the decrease in cell viability and the increase in cell death induced by radiotherapy were attenuated by CXCL12 treatment, and the inhibition of CXCR4 promoted colorectal cancer cells to be more sensitive to radiotherapy. We also examined the critical roles of CXCL12/CXCR4 in cell survival and found that radiotherapy induced Bax expression and facilitated the activity of caspase-3 and caspase-9, which were reversed by CXCL12 treatment. Cell apoptosis was enhanced by the inhibition of CXCR4 under radiotherapy conditions. Furthermore, treatment with CXCL12 resulted in an increased expression of survivin, and the inhibitory roles of CXCL12 in radiotherapy-induced apoptosis were mitigated by survivin knockdown. These results indicate that CXCL12/CXCR4 protects colorectal cancer cells against radiotherapy via survivin, implying an important underlying mechanism of resistance to radiotherapy during colorectal cancer therapy.

Using Computer-based Image Analysis to Improve Quantification of Lung Metastasis in the 4T1 Breast Cancer Model

10.3791/61805 ◽  
2020 ◽  
Author(s):  
Margaret A. Nagai-Singer ◽  
Alissa Hendricks-Wenger ◽  
Rebecca M. Brock ◽  
Holly A. Morrison ◽  
Juselyn D. Tupik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Image Analysis ◽  
Lung Metastasis ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Computer Based ◽  
4T1 Breast Cancer

scholarly journals Increased Expression of P-Glycoprotein Is Associated with Doxorubicin Chemoresistance in the Metastatic 4T1 Breast Cancer Model

2011 ◽  
Vol 178 (2) ◽  
pp. 838-852 ◽  
Author(s):  
Lili Bao ◽  
Aliyya Haque ◽  
Kamilah Jackson ◽  
Sidhartha Hazari ◽  
Krzysztof Moroz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Model ◽  
P Glycoprotein ◽  
Breast Cancer Model ◽  
4T1 Breast Cancer

scholarly journals CF750-A33scFv-Fc-Based Optical Imaging of Subcutaneous and Orthotopic Xenografts of GPA33-Positive Colorectal Cancer in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Danfeng Wei ◽  
Qing Fan ◽  
Huawei Cai ◽  
Hao Yang ◽  
Lin Wan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Optical Imaging ◽  
Near Infrared ◽  
Fluorescence Probe ◽  
Imaging System ◽  
Diagnostic Tools ◽  
Tumor Tissues ◽  
Colorectal Cancer Cells ◽  
Human Igg1 ◽  
Orthotopic Xenografts

Antibody-based imaging agents are attractive as adjuvant diagnostic tools for solid tumors. GPA33 is highly expressed in most human colorectal cancers and has been verified as a diagnostic and therapeutic target. Here, we built an A33scFv-Fc antibody against GPA33 by fusing A33scFv to the Fc fragment of human IgG1 antibodies. The A33scFv-Fc specifically binds GPA33-positive colorectal cancer cells and tumor tissues. After the intravenous injection of mice bearing subcutaneous GPA33-positive LS174T tumor grafts with near-infrared fluorescence probe CF750-labeled A33scFv-Fc (CF750-A33scFv-Fc), high contrast images of the tumor grafts could be kinetically documented within 24 h using an optical imaging system. However, GPA33-negative SMMC7721 tumor grafts could not be visualized by injecting the same amount of CF750-A33scFv-Fc. Moreover, in subcutaneous LS174T tumor-bearing mice, tissue scanning revealed that the CF750-A33scFv-Fc accumulated in the tumor grafts, other than the kidney and liver. In mice with orthotopic tumor transplantations, excrescent LS174T tumor tissues in the colon were successfully removed under guidance by CF750-A33scFv-Fc-based optical imaging. These results indicate that CF750-A33scFv-Fc can target GPA33, suggesting the potential of CF750-A33scFv-Fc as an imaging agent for the diagnosis of colorectal cancer.

scholarly journals Osteopontin binds ICOSL promoting tumor metastasis

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Davide Raineri ◽  
Chiara Dianzani ◽  
Giuseppe Cappellano ◽  
Federica Maione ◽  
Gianluca Baldanzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Metastasis ◽  
Immune Checkpoints ◽  
Cancer Model ◽  
Therapeutic Approaches ◽  
Breast Cancer Model ◽  
4T1 Breast Cancer ◽  
Anti Tumor Activity

Abstract ICOSL/ICOS are costimulatory molecules pertaining to immune checkpoints; their binding transduces signals having anti-tumor activity. Osteopontin (OPN) is here identified as a ligand for ICOSL. OPN binds a different domain from that used by ICOS, and the binding induces a conformational change in OPN, exposing domains that are relevant for its functions. Here we show that in vitro, ICOSL triggering by OPN induces cell migration, while inhibiting anchorage-independent cell growth. The mouse 4T1 breast cancer model confirms these data. In vivo, OPN-triggering of ICOSL increases angiogenesis and tumor metastatization. The findings shed new light on ICOSL function and indicate that another partner beside ICOS may be involved; they also provide a rationale for developing alternative therapeutic approaches targeting this molecular trio.

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