Down-regulation of NTSR3 inhibits cell growth and metastasis, as well as the PI3K–AKT and MAPK signaling pathways in colorectal cancer

2020 ◽  
Vol 98 (5) ◽  
pp. 548-555
Author(s):  
Aihua Liu ◽  
Zhongfu Zuo ◽  
Linlin Liu ◽  
Lihua Liu
Keyword(s):  
Colorectal Cancer ◽  
Cell Growth ◽  
Signaling Pathways ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mapk Signaling ◽  
Adhesion Assay ◽  
Caspase 9 ◽  
Down Regulation ◽  
Mapk Signaling Pathways

Colorectal cancer is a common malignancy. NTS receptor 3 (NTSR3) is known to play an important role in several cancers. This study examined the effects of NTSR3 on cell growth and metastasis in colorectal cancer. Western blot analysis, real-time PCR, immunofluorescence staining, MTT, cell cycle assay, cell apoptosis assay, Hoechst staining, caspase-3 and caspase-9 activity assays, cell adhesion assay, wound healing assay, and a Transwell assay were used in this study. We found that NTSR3 was expressed at relatively high levels in the colorectal cancer cell lines SW620 and SW480. NTSR3 knockdown suppressed cell growth and promoted cell apoptosis. Meanwhile, the protein expression levels of cyclinD1, cyclinE1, CDK4, and p-RB were reduced, and the levels of p-P27, P15, P21, cleaved caspase-3, and cleaved caspase-9 protein were increased. Cell invasiveness and cell migration were reduced with knockdown of NTSR3. In addition, our rescue experiments demonstrated that overexpression of the siRNA-resistant alleles of NTSR3 abrogated the NTSR3-siRNA-mediated effects on cell function. Further, down-regulation of NTSR3 inactivated the PI3K–AKT and MAPK signaling pathways. Collectively, these data demonstrate that knockdown of NTSR3 inhibits cell growth and metastasis, as well as the PI3K–AKT and MAPK signaling pathways in colorectal cancer. Thus, our results indicate that NTSR3 is a potential therapeutic target for treating colorectal cancer.

Temozolomide combined with the PI3K inhibitor LY294002 or the mTOR inhibitor rapamycin inhibits melanoma cell growth, survival and invasion

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8559-8559 ◽  
Author(s):  
F. E. Meier ◽  
K. Lasithiotakis ◽  
B. Schittek ◽  
T. Sinnberg ◽  
C. Garbe
Keyword(s):  
Cell Growth ◽  
Metastatic Melanoma ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Mtor Inhibitor ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Pi3k Inhibitor ◽  
Mapk Signaling Pathways

8559 Background: Potential therapeutic targets in the treatment of metastatic melanoma have emerged, to which pharmacological inhibitors have been designed, which may enhance tumor chemosensitivity. In melanoma, dacarbazine is considered to be the most effective agent although total responses do not exceed 20% The clinical activity of temozolomide is similar to that of dacarbazine, but temozolomide has the advantages of being absorbed orally and of crossing the blood-brain barrier. Many clinical trials of targeted therapy and chemotherapy combinations lack rigorous preclinical evaluation and may neglect relevant mechanistic interactions. The PI3K-AKT-mTOR (AKT) and RAS-RAF- MEK-ERK (MAPK) signaling pathways are constitutively activated in melanoma, and appear to play a role in chemoresistance. Methods: In this study, a panel of pharmacological inhibitors was utilized in order to block the AKT and MAPK signaling pathways at different levels (AKT: PI3K, mTOR; MAPK: RAF, MEK) in 5 human metastatic melanoma cell lines. The effects on chemosensitivity to temozolomide and cisplatin was then investigated. Results: The effects of most inhibitors on chemosensitivity varied significantly between the different cell lines. However, LY294002, a PI3K inhibitor and rapamycin, an mTOR inhibitor, consistently enhanced chemosensitivity. Treatment of melanoma cells with temozolomide or cisplatin combined with LY294002 or rapamycin had a strong effect on melanoma cell growth and survival. Invasive melanoma growth in organotypic cultures of human skin was suppressed completely. The most pronounced potentiation of efficacy was seen with temozolomide in combination with rapamycin. Conclusions: These data suggest that LY294002 and rapamycin can render melanoma cells susceptible to apoptosis, induced by chemotherapeutic agents such as temozolomide and cisplatin. Since both temozolomide and rapamycin are used clinically, the combination of temozolomide with rapamycin might potentially be utilized as an approach in melanoma treatment. This combination merits clinical investigation. No significant financial relationships to disclose.

scholarly journals Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

2021 ◽  
Vol 22 (19) ◽  
pp. 10260
Author(s):  
Constantin Stefani ◽  
Daniela Miricescu ◽  
Iulia-Ioana Stanescu-Spinu ◽  
Remus Iulian Nica ◽  
Maria Greabu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Pathogenesis ◽  
The Impact ◽  
Mapk Signaling Pathways

Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC.

In vitro and in vivo anti-inflammatory effects of different extracts from Epigynum auritum through down-regulation of NF-κB and MAPK signaling pathways

2020 ◽  
Vol 261 ◽  
pp. 113105
Author(s):  
Meilian Yang ◽  
Yudan Wang ◽  
Gopal Patel ◽  
Qingwang Xue ◽  
Guy Sedar Singor Njateng ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Mapk Signaling ◽  
Down Regulation ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways
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