scholarly journals Knockdown of PRDX2 sensitizes colon cancer cells to 5-FU by suppressing the PI3K/AKT signaling pathway

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Jun Xu ◽  
Shouru Zhang ◽  
Rong Wang ◽  
Xingye Wu ◽  
Li Zeng ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Cancer Resistance ◽  
Colon Cancer Cells ◽  
Akt Signaling Pathway ◽  
Ros Scavenging ◽  
Bax Protein

Although, 5-Fluorouracil (5-FU) remains widely used in adjuvant therapy in patients with colon cancer, resistance to 5-FU-based chemotherapy is an important reason for treatment failure. Recent studies have reported that an enhanced reactive oxygen species (ROS) scavenging system shows drug resistance to 5-FU. Peroxiredoxin-2 (PRDX2), is an important member of the ROS scavenging system, and may be a potential target that promotes chemosensitivity to 5-FU in colon cancer. Here, we depleted PRDX2 by PRDX2-shRNA-LV transduction in two colon cancer cell lines and found that in vitro PRDX2 knockdown facilitates cell death, and apoptosis in 5-FU-treated colon cancer cells. In addition, we found that PRDX2 depletion in mice treated with 5-FU resulted in, inhibition of tumor growth, compared with mice treated with 5-FU alone. Our data also suggested that the PI3K/AKT signaling pathway links PRDX2 with 5-FU-induced apoptosis in colon cancer. Furthermore, when PRDX2 was overexpressed in colon cancer cells, we found increased p-AKT protein expression and reduced Bcl-2/Bax protein expression. PRDX2 and p-AKT protein expression were analyzed by immunohistochemistry technology in human colon carcinoma tissues. Pearson correlation coefficient is 0.873 and P<0.05. PRDX2 depletion led to reduced p-AKT expression and PI3K/AKT pathway inhibition promoted cell apoptosis in HT29 cell line. Taken together, our study suggests that decreasing the expression of PRDX2 could be a promising strategy for increasing the sensitivity of colon cancer cells to 5-FU.

scholarly journals Angiomotin promotes the malignant potential of colon cancer cells by activating the YAP-ERK/PI3K-AKT signaling pathway

2016 ◽  
Vol 36 (6) ◽  
pp. 3619-3626 ◽  
Author(s):  
Yan Zhang ◽  
Jun Yuan ◽  
Xinli Zhang ◽  
Futang Yan ◽  
Minggang Huang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Malignant Potential ◽  
Colon Cancer Cells ◽  
Akt Signaling Pathway

scholarly journals siPRDX2-elevated DNM3 inhibits the proliferation and metastasis of colon cancer cells via AKT signaling pathway

2019 ◽  
Vol Volume 11 ◽  
pp. 5799-5811 ◽  
Author(s):  
Yini Ma ◽  
Liying Guan ◽  
Yanxin Han ◽  
Yi Zhou ◽  
Xiaoming Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Colon Cancer Cells ◽  
Akt Signaling Pathway ◽  
Proliferation And Metastasis

scholarly journals MACC1 facilitates chemoresistance and cancer stem cell-like properties of colon cancer cells through the PI3K/AKT signaling pathway

2017 ◽  
Vol 16 (6) ◽  
pp. 8747-8754 ◽  
Author(s):  
Jiankai Wang ◽  
Wenjuan Wang ◽  
Hongyi Cai ◽  
Binbin Du ◽  
Lijuan Zhang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Colon Cancer Cells ◽  
Akt Signaling Pathway

scholarly journals Asiatic Acid Interferes with Invasion and Proliferation of Breast Cancer Cells by Inhibiting WAVE3 Activation through PI3K/AKT Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiao-jun Gou ◽  
Huan-huan Bai ◽  
Li-wei Liu ◽  
Hong-yu Chen ◽  
Qi Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Nude Mice ◽  
Breast Cancer Cells ◽  
Akt Signaling ◽  
Asiatic Acid ◽  
Akt Signaling Pathway ◽  
Xenografted Tumor

Objective. To explore the ability of asiatic acid to interfere with the invasion and proliferation of breast cancer cells by inhibiting WAVE3 expression and activation through the PI3K/AKT signaling pathway. Methods. The MDA-MB-231 cells with strong invasiveness were screened by transwell assay, and plasmids with high expression of WAVE3 were constructed for transfection. The transfection effect and protein expression level of plasmids were verified by PCR and WB. The effects of asiatic acid on cell proliferation and invasion were investigated by flow cytometry. The xenografted tumor models in nude mice were established to study the antitumor activity of asiatic acid. Results. Asiatic acid significantly inhibited the activity of MDA-MB-231 cells, and the expression level of WAVE3 increased significantly in the tissue of ductal carcinoma in situ and was lower than that in the metastasis group. After plasmid transfection, the mRNA and protein expression of WAVE3 increased significantly in the cells. Asiatic acid at different concentrations had an impact on cell apoptosis and invasion and could significantly inhibit the expression of WAVE3, P53, p-PI3K, p-AKT, and other proteins. The T/C(%) of asiatic acid (50 mg/kg) for MDA-MB-231(F10) xenografted tumor in nude mice was 46.33%, with a tumor inhibition rate of 59.55%. Asiatic acid could significantly inhibit the growth of MDA-MB-231 (F10) xenografted tumors in nude mice (p<0.05). Conclusions. Asiatic acid interferes with the ability of breast cancer cells to invade and proliferate by inhibiting WAVE3 expression and activation and the mechanism of action may be related to the PI3K/AKT signaling pathway.

scholarly journals Fibroblast-derived CXCL12 regulates PTEN expression and is associated with the proliferation and invasion of colon cancer cells via PI3k/Akt signaling

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Jiachi Ma ◽  
Xiaowen Sun ◽  
Yimin Wang ◽  
Bangling Chen ◽  
Liyu Qian ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Stromal Cells ◽  
Metastatic Potential ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Colon Cancer Cells ◽  
Proliferation And Invasion

Abstract Background Stromal-derived CXCL12 play an important role which influence the proliferation and invasiveness of colon cancer in microenvironment. The present study aimed to analyze the underlying mechanism by which CXCL12 and tumour suppressor protein phosphatase and tensin homologue deleted on chromosome 10 (PTEN) influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells. Methods RT-PCR and western blot were detected the expression of CXCL12, CXCR4 and PTEN in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and PTEN on proliferation and invasion of colon cancer cells were evaluated by real-time PCR, proliferation and invasion assays using an in vitro system consisting of co-cultured cancer cells and stromal cells. We eventually investigated activation of PI3K/Akt signaling by CXCL12 regulate PTEN and involved in the metastatic process of colon cancer. In addition, we also examine how the knockdown of PTEN influences proliferation and invasion and correlate with CXCL12/CXCR4/PI3K/Akt, determination of PTEN up-down-stream targets that preferentially contribute to tumorigenesis. Results Blockage of PTEN phosphorylation led to a stronger enhancement of cell proliferation and invasion upon stimulation with CXCL12 via its activation of the PI3K/Akt signaling pathway. Furthermore, knockdown of PTEN by siRNA transfection was also found to enhance the activation of the PI3K/Akt pathway, thereby promoting cell invasion and proliferation. CXCL12 induced transcriptional down-regulation of activated PTEN and this signaling pathway promotes cell survival. CXCL12/CXCR4/PI3K/Akt cascade may be critical for colon cancer cells to metastasize. Conclusions Based on our results, we suggest that the modification of CXCR4, PTEN, or PI3K function might be promising new therapeutic approaches to inhibit the aggressive spread of colon cancer.

scholarly journals TUSC3 inhibits cell proliferation and invasion in cervical squamous cell carcinoma via suppression of the AKT signaling pathway

2021 ◽  
Author(s):  
Fei Sun ◽  
Qiuling Jie ◽  
Qi Li ◽  
Yunjian Wei ◽  
Ping Long ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cervical Squamous Cell Carcinoma ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Proliferation And Invasion

Abstract Background The expression of tumor suppressor candidate 3 (TUSC3) is associated with proliferation in several types of cancer, leading to an unfavorable prognosis. The present study aimed to assess the cellular and molecular function of TUSC3 in patients with cervical squamous cell carcinoma (CSCC). Methods Levels of mRNA expressions of TUSC3 were analyzed in CSCC tissues and six cell lines using qRT-PCR. Immunohistochemistry(IHC) was used to evaluate the protein expression level of TUSC3 in four paired specimens, 220 paraffin-embedded CSCC specimens and 60 cases of normal cervical tissues(NCTs), respectively. Short hairpin RNA interference was employed for TUSC3 knockdown. Cell proliferation, migration and invasion was evaluated using growth curve, MTT assay, wound healing and transwell assay respectively. Results The results demonstrated that TUSC3 mRNA and protein expression levels were down-regulated in CSCC samples. Multivariate and univariate analyses indicated that TUSC3 was an independent prognostic factor for patients with CSCC. Decreased TUSC3 expression levels were significantly associated with proliferation and an aggressive phenotype of cervical cancer cells. Moreover, the knockdown of TUSC3 promoted migration and invasion of cancer cells, while the increased expression of TUSC3 exhibited the opposite effects. The down-regulation of TUSC3 facilitated proliferation and invasion of CSCC cells through the activation of the AKT signaling pathway. Conclusions Our data demonstrated that the down-regulation of TUSC3 promoted CSCC cell metastasis via the AKT signaling pathway. Therefore, TUSC3 may serve as a novel prognostic marker and potential target for CSCC.

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