Expression of 3-phosphoinositide-dependent protein kinase 1 in colorectal cancer as a potential therapeutic target

Xu, Zefeng; Liao, Bihong; Zhang, Ru; Yao, Jun; Shi, Rui-Yue; Wang, Lisheng

doi:10.1007/s12032-015-0645-4

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…3‐phosphoinositide‐dependent protein kinase 1 (PDK1) is the first node of the PI3K signal output since it phosphorylates the AKT at Thr308 site which is a prerequisite for full activation of AKT 7 . Elevated expression of PDK1 was observed in various human cancers such as breast cancer, 8 colorectal carcinoma, 9 esophageal carcinoma, 10 and hepatocellular carcinoma, 11 and overexpression of PDK1 was associated with poor prognosis of these tumors. In addition, PDK1 plays an important role in many cellular processes including cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) 12 .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of PDK1 enhances radiosensitivity and reverses epithelial–mesenchymal transition in nasopharyngeal carcinoma

et al. 2022

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Background Radioresistance challenges the clinical outcomes of nasopharyngeal carcinoma (NPC). The 3‐phosphoinositide‐dependent protein kinase 1 (PDK1) is a crucial kinase of PI3K/AKT signaling pathway which has been implicated in the process of radioresistance. However, the role of PDK1 in NPC remains largely unclear. Methods The expression of PDK1 was determined by immunohistochemistry and Western blot. The effects of RNA interference and pharmacologic inhibitor of PDK1 in combination with irradiation were investigated. Results Overexpression of PDK1 was correlated with poor prognosis in patients with NPC. PDK1 depletion enhanced radiosensitivity of NPC cells both in vitro and in vivo. Additionally, a specific PDK1 inhibitor also had the potential to enhance radiosensitivity in radioresistant NPC cells. Mechanistically, PDK1 depletion inhibited various targets of AKT including mTOR and GSK‐3β and reversed the epithelial–mesenchymal transition. Conclusions These findings indicated that PDK1 might be a potential target for NPC.

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Section: Introductionmentioning

confidence: 99%

Inhibition of PDK1 enhances radiosensitivity and reverses epithelial–mesenchymal transition in nasopharyngeal carcinoma

et al. 2022

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“…PDK1 has been implicated in cancer progression, including proliferation, apoptosis and invasion and involved in signaling pathways altered in cancer, such as PI3K/Akt, Ras/MAPK and Myc (19). Moreover, over-expression of PDK1 was observed at both mRNA and protein levels in CRC specimens and cell lines (20). Thus, targeting PDK1 provides great therapeutic strategy for CRC.…”

Section: Discussionmentioning

confidence: 99%

An Integrated Network, RNA Sequencing, and Experiment Pharmacology Approach Reveals the Active Component, Potential Target, and Mechanism of Gelsemium elegans in the Treatment of Colorectal Cancer

Wang

Liang

et al. 2020

Front. Oncol.

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In this study, a combination of network pharmacology, bioinformatics analysis, molecular docking and transcriptomics was used to investigate the active ingredient and potential target of Gelsemium elegans in the treatment of colorectal cancer. Koumine was screened as the active component by targeting PDK1 through network pharmacology and reverse docking. RNA-Seq, enrichment analysis and validation experiment were then further employed to reveal koumine might function in inhibiting Akt/mTOR/HK2 pathway to regulate cell glycolysis and detachment of HK2 from mitochondria and VDAC-1 to activate cell apoptosis both in vitro and in vivo. In the present study, we provide a systematical approach for the identification of effective ingredient and potential target of herbal medicine. Our results have important implication for the intensive study of koumine as novel anticancer agents for colorectal cancer and could be supportive in its further structural modification.

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“…The claim is supported by a report that high levels of prostaglandin in-vitro and in-vivo inhibit cancer growth. Mitogen Activated Protein Kinase-3 (MAPK) and 3-Phosphoinositide-Dependent Protein Kinase 1 (PDK-1) are some of the most studied COX-independent pathways in CRC oncogenesis [15,16].…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Drugs for Colorectal Cancer Chemoprevention through Computational Analysis

Kioko¹,

Kagia²

2023

austinjpharmacolther

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Introduction: Colorectal cancer is one of the common causes of hospitalizations, readmission, and poor quality of life due to disability, pain, and death. Most drugs identified to provide chemoprevention in colorectal cancer, such as NSAIDs, have a high level of toxicity. There is need to find novel drugs targeting colorectal cancer with favorable clinical profiles. Objective: The study aimed to identify possible colorectal cancer prevention drugs by comparing the docking scores (representing potential biologic activity) of Aspirin, Sulindac, and Celecoxib with their structurally similar analogs. Materials and Methods: Ligand-based virtual screening and structure-based virtual screening were done for aspirin, sulindac and celecoxib to identify potential drug-like compounds. Compounds that passed the screening, pharmacokinetic profiling, and toxicity testing were considered possible drugs for colorectal cancer chemoprevention. Results: The study identified 7 drug-like compounds from the ZINC database. ZINC02570895, with a better docking score than celecoxib coupled with favorable toxicity and metabolic profiles, was the most appropriate drug candidate for the inhibition of PDK-1. ZINC22309227, with a better docking score and favorable pharmacokinetic profile than sulindac was the most appropriate compound for further development into a MAP Kinase inhibitor. ZINC39406706, ZINC26469982, ZINC01847506, ZINC3382343, and ZINC01682308 had favorable toxicity profiles compared to aspirin and were most suitable for development of cyclooxygenase inhibitors in colorectal cancer prevention. Conclusion: In-vivo and in-vitro tests are needed to ascertain the biological activity, synthesizability and clinical use of the compounds.

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Expression of 3-phosphoinositide-dependent protein kinase 1 in colorectal cancer as a potential therapeutic target

Cited by 5 publications

References 38 publications

Inhibition of PDK1 enhances radiosensitivity and reverses epithelial–mesenchymal transition in nasopharyngeal carcinoma

Inhibition of PDK1 enhances radiosensitivity and reverses epithelial–mesenchymal transition in nasopharyngeal carcinoma

An Integrated Network, RNA Sequencing, and Experiment Pharmacology Approach Reveals the Active Component, Potential Target, and Mechanism of Gelsemium elegans in the Treatment of Colorectal Cancer

Identification of Potential Drugs for Colorectal Cancer Chemoprevention through Computational Analysis

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