CDK2-AP1 inhibits growth of breast cancer cells by regulating cell cycle and increasing docetaxel sensitivity in vivo and in vitro

He, Xiangming; Xiang, Hua; Zong, Xiangyun; Yan, Xuebing; Yang, Yu; Guan, Lan; Zou, Dayang; Yang, Hongjian

doi:10.1186/s12935-014-0130-8

Cited by 24 publications

(16 citation statements)

References 17 publications

(14 reference statements)

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“…Furthermore, pharmacological concentrations of ascorbate could radiosensitize glioblastoma multiforme primary cells by increasing oxidative DNA damage and inhibiting G2/M arrest 35. Unlike the observed increase in cell cycle progression from G1 to S phase driven by cyclin D1, He et al36 found that in breast cancer cells, upregulation of cyclin-dependent kinase 2 associate protein-1 (CDK2AP1) caused cell cycle arrest in G2/M phase and cell division was inhibited. At the same time, there was inverse correlation between CDK2/cyclin D1 and CDK2AP1 expressions.…”

Section: Discussionmentioning

confidence: 99%

<p>Effects of combined inhibition of STAT3 and VEGFR2 pathways on the radiosensitivity of non-small-cell lung cancer cells</p>

Zhuang

et al. 2019

OTT

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PurposeThe goals of this study were to determine the effects of combined inhibition of STAT3 and vascular endothelial growth factor receptor 2 (VEGFR2) pathways on the radiosensitivity of non-small-cell lung cancer (NSCLC) cells, and to assess the underlying mechanisms.MethodsThe expressions of VEGFR2, STAT3, related signaling molecules, hypoxia-inducible factor 1-alpha (HIF-1α), and cyclin D1 were determined by Western blotting. Radiosensitivity was assessed using the colony-forming assay, and cell cycle and cell death were analyzed by flow cytometry. A nude mouse xenograft tumor model of Calu-1 cells was established. The hepatorenal toxicity of the above-mentioned treatment on tumor-bearing mice was observed by H&E staining. The expression of STAT3, VEGFR2, HIF-1α, and cyclin D1 of the transplanted tumor tissues was detected by immunohistochemistry. Apoptosis of tumor tissues was evaluated by TUNEL staining.ResultsIn vitro, we selected two cell lines with high expression levels of STAT3, including Calu-1 cells that exhibit high VEGFR2 expression and A549 cells that exhibit low VEGFR2 expression. When apatinib treatment was combined with S3I-201, the expression of VEGFR2, STAT3, and their downstream signaling molecules was significantly decreased (P<0.01). There was an increase in cell death and G2/M phase arrest after treatments, with the most significant changes occurring upon dual inhibition of STAT3 and VEGFR2 (P<0.01). In vivo, combined treatment of radiotherapy and dual inhibition of VEGFR2 and STAT3 was well tolerated and did not deliver additional toxicity. Compared with the control group and the radiation treatment (RT) + apatinib or RT + S3I-201 duplex group, the expression level of STAT3, p-STAT3, VEGFR2, HIF-1α, and cyclin D1 in the triple group (RT + apatinib + S3I-201) was the lowest, and the proportion of apoptotic cells was the highest (P<0.05).ConclusionThe combined inhibition of VEGFR2 and STAT3 is effective in enhancing radiosensitizing effects in NSCLC cells.

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Section: Discussionmentioning

confidence: 99%

<p>Effects of combined inhibition of STAT3 and VEGFR2 pathways on the radiosensitivity of non-small-cell lung cancer cells</p>

Zhuang

et al. 2019

OTT

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“…Our observations are in accordance with a wealth of laboratory studies supporting the notion that CDK2AP1 behaves as a tumour-suppressor gene in a variety of tumours (12)(13)(14)(15)(16)(17)(18)(19). Zou et al reported that CDK2AP1 inhibited the proliferation of breast cancer cells and the in vivo growth of tumour cells (15).…”

Section: Discussionsupporting

confidence: 91%

“…CDK2AP1 knockdown resulted in enhanced colony formation and cell growth. It also inhibited the growth of breast cancer cells through regulation of the cell cycle and increased in vitro and in vivo sensitivity to docetaxel (16).…”

Section: Discussionmentioning

confidence: 99%

mRNA Expression of CDK2AP1 in Human Breast Cancer: Correlation with Clinical and Pathological Parameters

Gera

Mokbel

Jiang

et al. 2018

Cancer Genomics Proteomics

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Background: Cyclin-dependent kinase 2associated protein 1 (CDK2AP1) interacts with CDK2AP2, modulates the actions of transforming growth factor-B1, cyclin-dependent kinase 2 and retinoblastoma protein, and closely interacts with micro-RNA21 and micro-RNA25. Our objective was to determine if CDK2AP1 mRNA expression levels were consistent with tumour-suppressive functions in breast cancer. Materials and Methods: A total of 134 samples were analysed. CDK2AP1 mRNA levels were measured using quantitative polymerase chain reaction (RT-PCR) and normalised against glyceraldehyde 3-phosphate dehydrogenase mRNA. Levels in breast cancer and adjacent non-cancerous breast tissue were analysed against pathological and clinical parameters (TNM staging, survival over a 10-year follow-up period). Results: Normalised CDK2AP1 expression was 38-fold higher in adjacent noncancerous breast tissue than in breast cancer. CDK2AP1 expression in disease-free patients at 10 years was more than threefold that of patients who died of breast cancer. However, neither of these differences in expression levels reached statistical significance. CDK2AP1 mRNA levels were higher in TNM1 compared to TNM3 (p=0.016) and with TNM4 (p=0.016). There were no significant associations between CDK2AP1 expression and estrogen receptor status, tumour grade and tumour type. There was no significant difference in overall survival between patients with high and those with low CDK2AP1 mRNA levels after a median follow-up of 10 years (Kaplan-Meier analysis, p=0.872). Conclusion: To our knowledge, this is the first study in the literature to examine the mRNA expression of CDK2AP1 in human breast cancer over a long-term follow-up period. A compelling relationship exists between high CDK2AP1 mRNA expression and lower TNM classification of breast cancer, which is consistent with CDK2AP1 having a tumoursuppressive function. Cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) is hypothesised to be a tumour suppressor which works through the mediation of several other genes and proteins. First discovered in 1995 as 'deleted in oral cancer-1' (DOC1) gene (1), investigators have since found evidence for its growth-/tumour-suppressive action and confirmed it to be likely implicated in the development of many cancer types (2, 3). CDK2AP1 and its associated homolog CDK2AP2 likely work together to effectively suppress cell growth due to their probable structural and functional relation (4); CDK2AP2 is a known tumour suppressor (5) which we previously investigated and provided evidence for its tumour-suppressive function in human breast cancer. The interaction between the two was recorded by using CDK2AP1 as 'bait' in liver cDNA screening and was verified both in vitro and in cells (6). Multiple investigations have been conducted regarding the relationship between different micro-RNAs (miRs) and CDK2AP1. Using cells taken from the tumour-free surgical margins of 18 patients with head and neck squamous cell carcinomas, miR-21 was found to be inversely correlated with CDK2AP1 a...

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“…25 When CDKs are abnormally up-regulated, cells undergo cycles and generate resistance to apoptosis, which result in uncontrolled proliferation. 26 CDK2, a member of the CDK family, is a serine/threonine protein kinase. It regulates cell cycle conversion of G1-and S-phase.…”

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confidence: 99%

The soy-derived peptide Vglycin inhibits the growth of colon cancer cells in vitro and in vivo

Gao

Sun

Xie

et al. 2017

Exp Biol Med (Maywood)

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The antidiabetic properties and the capability of inducing differentiation of human colon adenocarcinoma cells of Vglycin have been reported in our previous studies. However, the anticancer potential of Vglycin on colon cancer cells and its possible related mechanisms were still unknown. In this study, we found that Vglycin could reduce growth, viability, and colony formation or colony size of CT-26, SW480, and NCL-H716 colon cancer cells. Moreover, Vglycin decreased tumor volume by 38% in xenograft mice transplanted with CT-26 cells. The mechanisms of these phenomena may be due to the down-regulated CDK2 and Cyclin D1, G1/S phase cell cycle arrest, and the dysregulated expression of Bax, Bcl-2, and Mcl-1.The findings highlight the anticancer potential of Vglycin against colon cancer cells, and suggest Vglycin may be another colon cancer potential suppressive component of plant-derived peptides. AbstractVglycin, a novel natural polypeptide isolated from pea seeds, possesses antidiabetic properties. Our previous studies have shown that Vglycin can induce the differentiation of human colon adenocarcinoma cells. We aimed to determine the anticancer activity of Vglycin against colon cancer cells and to elucidate related apoptosis-inducing mechanisms. Treatment with purified Vglycin significantly reduced growth, viability, and colony formation of CT-26, SW480, and NCL-H716 colon cancer cells in a dose-dependent manner while down-regulating the expression of proliferating cell nuclear antigen. Mouse xenograft studies showed a 38% inhibition of colon cancer growth in mice treated with Vglycin (20 mg/kg/ day) at day 21. Furthermore, the potential mechanisms involved in Vglycin-induced cell apoptosis were examined using cell cycle studies, ultrastructural examination, as well as apoptosis-associated pathway analysis. The results showed that Vglycin significantly promoted apoptosis and G1/S phase cell cycle arrest. As revealed by Western blot, the expression of CDK2 and Cyclin D1 was down-regulated in all three Vglycin-treated colon cancer cells, indicating that the CDK2/Cyclin D1 cell cycle pathway involved in the initiation and progression of colon cancer. Moreover, the inhibition of Vglycin-induced cell proliferation in colon cancer cells was accompanied by alteration of the expression levels of the apoptosisrelated proteins Bax, Bcl-2 and Mcl-1, and an increase of caspase-3 activity. Together, our results suggest that Vglycin may be another plant-derived peptide that suppresses colon cancer, supporting the continued investigation of Vglycin as therapeutic agent for colon cancer.

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CDK2-AP1 inhibits growth of breast cancer cells by regulating cell cycle and increasing docetaxel sensitivity in vivo and in vitro

Cited by 24 publications

References 17 publications

<p>Effects of combined inhibition of STAT3 and VEGFR2 pathways on the radiosensitivity of non-small-cell lung cancer cells</p>

<p>Effects of combined inhibition of STAT3 and VEGFR2 pathways on the radiosensitivity of non-small-cell lung cancer cells</p>

mRNA Expression of CDK2AP1 in Human Breast Cancer: Correlation with Clinical and Pathological Parameters

The soy-derived peptide Vglycin inhibits the growth of colon cancer cells in vitro and in vivo

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