The expression and clinical significance of PI3K, pAkt and VEGF in colon cancer

Zhang, Yinxu; Liu, Xiaomei; Zhang, Junhua; Li, Leiyu; Liu, Chunying

doi:10.3892/ol.2012.822

Cited by 28 publications

(25 citation statements)

References 12 publications

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“…Subsequently, analysis of the influence of miR-29c on NSCLC cell activities demonstrated that overexpression of miR-29c was able to inhibit the proliferation and promote the apoptosis of NSCLC cells. Since high expression of VEGFA has been reported to be correlated with the proliferation and metastasis of various types of tumor (11), it was hypothesized that miR-29c may regulate NSCLC cell activities by targeting VEGFA. Through bioinformatics analysis, it was predicted that VEGFA may be a direct target for miR-29c.…”

Section: Discussionmentioning

confidence: 99%

“…One of the primary factors in tumor angiogenesis stimulation is vascular endothelial growth factor A (VEGFA) (10). According to previous research, high expression of VEGF is associated with the proliferation and metastasis of several types of cancer (11). Through bioinformatics methods, it was identified that VEGFA may be a gene target for miR-29c.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-29c inhibits proliferation and promotes apoptosis in non-small cell lung cancer cells by targeting VEGFA

2018

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Non-small cell lung cancer (NSCLC) is a primary sub-type of lung cancer with a high incidence rate and poor prognosis. The primary therapeutic treatment for NSCLC is chemotherapy, which is considered to be ineffective and excessively toxic. Novel therapeutic methods, particularly molecular targeted therapy, have attracted considerable attention. MicroRNAs (miRs) are reported to be potential biomarkers and targeted agents with roles in various types of tumors. Herein, the present study presented the observation of aberrant low expression of miR‑29c and associated overexpression of vascular endothelial growth factor A (VEGFA) in NSCLC tumor tissues. The effects of miR‑29c upon NSCLC tumor progression, including cell proliferation and cellular apoptosis, were investigated. The possible regulatory mechanism of action of miR‑29c on its direct target VEGFA and the phosphatidylinositol 3‑kinase (PI3K)/RAC‑α serine/threonine‑protein kinase (Akt) signaling pathway was examined using multiple methods, including reverse transcription-quantitative polymerase chain reaction analysis, dual luciferase assay and western blot analysis. The results demonstrated that miR‑29c expression was downregulated in NSCLC tumor tissues compared with normal tissues. A marked negative correlation in the expression of miR‑29c and VEGFA was observed in clinical NSCLC tissues and cultured NSCLC cells. Overexpression of miR‑29c may inhibit cell proliferation and accelerate the cellular apoptosis rate of NSCLC tumor cells. Furthermore, the overexpression of miR‑29c was demonstrated to be able to downregulate the expression levels of VEGFA and PI3K/Akt signaling pathway‑associated proteins. The results of the present study suggested that miR‑29c might regulate NSCLC tumor progression by targeting VEGFA.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA-29c inhibits proliferation and promotes apoptosis in non-small cell lung cancer cells by targeting VEGFA

2018

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“…This model is in agreement with recent clinical studies reporting that PI3K and pAkt are highly expressed in colon cancer tissues. 31 IGF ligands and IGF1Rs are expressed in most, if not all, tissues in mammals and in zebrafish. 32,33 How is the ubiquitous IGF signaling system activated exclusively in NaR cells under low [Ca 2 þ ] environments?…”

Section: Discussionmentioning

confidence: 99%

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

et al. 2013

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Calcium deficiency causes abnormal colonic growth and increases colon cancer risk with poorly understood mechanisms. Here we elucidate a novel signaling mechanism underlying the Ca 2 þ deficiency-induced epithelial proliferation using a unique animal model. The zebrafish larval yolk sac skin contains a group of Ca 2 þ -transporting epithelial cells known as ionocytes. Their number and density increases dramatically when acclimated to low [Ca 2 þ ] environments. BrdU pulse-labeling experiments suggest that low [Ca 2 þ ] stimulates pre-existing ionocytes to re-enter the cell cycle. Low [Ca 2 þ ] treatment results in a robust and sustained activation of IGF1R-PI3K-Akt signaling in these cells exclusively. These ionocytes specifically express Igfbp5a, a high-affinity and specific binding protein for insulin-like growth factors (IGFs) and the Ca 2 þ -selective channel Trpv5/6. Inhibition or knockdown of Igfbp5a, IGF1 receptor, PI3K, and Akt attenuates low [Ca 2 þ ]-induced ionocyte proliferation. The role of Trpv5/6 was investigated using a genetic mutant, targeted knockdown, and pharmacological inhibition. Loss-of-Trpv5/6 function or expression results in elevated pAkt levels and increased ionocyte proliferation under normal [Ca 2 þ ]. These increases are eliminated in the presence of an IGF1R inhibitor, suggesting that Trpv5/6 represses IGF1R-PI3K-Akt signaling under normal [Ca 2 þ ]. Intriguingly, blockade of Trpv5/6 activity inhibits the low [Ca 2 þ ]-induced activation of Akt. Mechanistic analyses reveal that the low [Ca 2 þ ]-induced IGF signaling is mediated through Trpv5/6-associated membrane depolarization. Low extracellular [Ca 2 þ ] results in a similar amplification of IGF-induced PI3K-PDK1-Akt signaling in human colon cancer cells in a TRPV6-dependent manner. These results uncover a novel and evolutionarily conserved signaling mechanism that contributes to the abnormal epithelial proliferation associated with Ca 2 þ deficiency.

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“…VEGF (vascular endothelial growth factor), as a major pro-angiogenic factor in tumor tissues, can directly stimulate the proliferation of endothelial cells by specific receptors on them, to produce the plasminogen activator and collagenase, etc., increase vascular permeability, and promote plasma fibrinogen extravasation. This can not only promote the migration of endothelial cells, helping angiogenesis, but also be conducive to tumor cell shedding, invasion or diffusion to adjacent matrix of fibrous and connective tissues, so as to create the conditions for tumor invasion and metastasis [19][20][21]. Colon cancer is a malignant tumor with rich blood supply and high metastasis, and its tumor angiogenesis, proliferation, invasion and metastasis are closely related to VEGF [22][23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Effects of Apigenin on the Expressions of TGF-β1R II, NF-κB and VEGF Genes in Tumor Tissues of Mice with H29 Colon Cancer

Yi¹

2015

AJCEM

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To observe the effects of Apigenin on the expressions of TGF-β1R II, NF-κB and VEGF genes in tumor tissues of mice with H29 colon cancer. Fifty ICR mice with H29 colon cancer were randomly divided into five groups: normal saline group, low-dose Apigenin group, middle-dose Apigenin group and high-dose Apigenin group and cyclophosphamide group. The mice were killed on the next day of administration discontinuance, and subcutaneous tumor tissues were collected. Quantitative fluorescence RT-PCR was used to detect the expression of TGF-β1R II, NF-κB and VEGF genes in tumor tissues of H29 colon cancer mice. Apigenin raised the expression level of TGF-β1R II in H29 colon cancer tissues, which showed the most obvious effect in the middle-dose group, with a significant difference compared with the normal saline group (P<0.01). The Apigenin group of each dose could significantly lower the NF-κB expression level in H29 colon solid tumors, showing significant differences compared with the normal saline group (P<0.01). The middle-dose and high-dose Apigenin groups could significantly reduce the level of VEGF expression in tumor tissues of ICR mice with H29 colon cancer, and the high-dose group had most obvious effect, and there were significant difference among the middle-dose group, high-dose group and the normal saline group (P<0.01). The mechanism of anti-tumor effect of Apigenin might be the reason that Apigenin can raise the expression level of TGF-β1R II by down-regulating the expression of NF-κB and VEGF in tumor tissues of tumor-bearing mice, thereby inhibiting tumor angiogenesis and tumor cell proliferation, so as to achieve the anti-tumor effect.

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The expression and clinical significance of PI3K, pAkt and VEGF in colon cancer

Cited by 28 publications

References 12 publications

MicroRNA-29c inhibits proliferation and promotes apoptosis in non-small cell lung cancer cells by targeting VEGFA

MicroRNA-29c inhibits proliferation and promotes apoptosis in non-small cell lung cancer cells by targeting VEGFA

Calcium deficiency-induced and TRP channel-regulated IGF1R-PI3K-Akt signaling regulates abnormal epithelial cell proliferation

Effects of Apigenin on the Expressions of TGF-β1R II, NF-κB and VEGF Genes in Tumor Tissues of Mice with H29 Colon Cancer

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