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Search Results (51)
  • Open Access

    REVIEW

    PI3K/AKT signaling pathway as a critical regulator of Cisplatin response in tumor cells

    ZAHRA NASRPOUR NAVAEI1, GHAZALEH KHALILI-TANHA1, AMIR SADRA ZANGOUEI2, MOHAMMAD REZA ABBASZADEGAN3, MEYSAM MOGHBELI1,3,*

    Oncology Research, Vol.29, No.4, pp. 235-250, 2021, DOI:10.32604/or.2022.025323

    Abstract Chemotherapy is one of the main therapeutic modalities for cancer patients. Cisplatin (CDDP), as one of the first-line drugs, is of great importance in the chemotherapy of various tumors. However, a significant percentage of cancer patients are resistant to CDDP treatment. Due to the CDDP side effects on normal tissues, the diagnosis of CDDP resistance is required to suggest the most efficient therapeutic strategies for cancer patients. Several molecular mechanisms and signaling pathways are associated with CDDP response. The PI3K/AKT signaling pathway has a pivotal role in the transmission of extracellular signals into the cells to regulate various pathophysiological processes… More >

  • Open Access

    ARTICLE

    Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt

    HASSAN M. OTIFI1, MISHARI ALSHYARBA2, MAJED AL FAYI3,4, AYED A. DERA3,4, PRASANNA RAJAGOPALAN3,4,*

    Oncology Research, Vol.29, No.3, pp. 217-227, 2021, DOI:10.32604/or.2022.03570

    Abstract Targeted therapies are gaining global attention to tackle Renal Cancer (RC). This study aims to screen FPMXY- 14 (novel arylidene analogue) for Akt inhibition by computational and in vitro methods. FPMXY-14 was subjected to proton NMR analysis and Mass spectrum analysis. Vero, HEK-293, Caki-1, and A498 cell lines were used. Akt enzyme inhibition was studied with the fluorescent-based kit assay. Modeller 9.19, Schrodinger 2018-1, LigPrep module, and Glide docking were used in computational analysis. The nuclear status was assessed by PI/Hoechst- 333258 staining, cell cycle, and apoptosis assays were performed using flow cytometry. Scratch wound and migrations assays were performed.… More >

  • Open Access

    ARTICLE

    Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells

    MESFER AL SHAHRANI1,2,*, PRASANNA RAJAGOPALAN1,2, MOHAMMAD ABOHASSAN1, MOHAMMAD ALSHAHRANI1, YASSER ALRAEY1, REEM M. GAHTANI1, SURESH RADHAKRISHNAN3, KHLOOD DAGREERY4

    Oncology Research, Vol.29, No.3, pp. 149-157, 2021, DOI:10.32604/or.2022.03539

    Abstract Estrogen receptor (ER) α is expressed in a subset of patient-derived acute myeloid leukemia (AML) cells, whereas Akt is predominantly expressed in most types of AML. Targeting AML with dual inhibitors is a novel approach to combat the disease. Herein, we examined a novel small molecule, 3-(4-isopropyl) benzylidene-8-ethoxy,6- methyl, chroman-4-one (SBL-060), capable of targeting AML cells by inhibiting ERα and Akt kinase. The chemical properties of SBL-060 were identified by proton nuclear magnetic resonance (1 H-NMR), 13C-NMR, and mass spectroscopy. In silico docking was performed using an automated protocol with AutoDock-VINA. THP-1 and HL-60 cell lines were differentiated using phorbol… More >

  • Open Access

    ARTICLE

    Liquiritigenin Inhibits Colorectal Cancer Proliferation, Invasion, and Epithelial-to-Mesenchymal Transition by Decreasing Expression of Runt-Related Transcription Factor 2

    Fan-Chun Meng, Jun-Kai Lin

    Oncology Research, Vol.27, No.2, pp. 139-146, 2019, DOI:10.3727/096504018X15185747911701

    Abstract Inhibition of tumor metastasis is one of the most important purposes in colorectal cancer (CRC) treatment. This study aimed to explore the effects of liquiritigenin, a flavonoid extracted from the roots of Glycyrrhiza uralensis Fisch, on HCT116 cell proliferation, invasion, and epithelial-to-mesenchymal transition (EMT). We found that liquiritigenin significantly inhibited HCT116 cell proliferation, invasion, and the EMT process, but had no influence on cell apoptosis. Moreover, liquiritigenin remarkably reduced the expression of runt-related transcription factor 2 (Runx2) in HCT116 cells. Overexpression of Runx2 obviously reversed the liquiritigenininduced invasion and EMT inhibition. Furthermore, liquiritigenin inactivated the phosphoinositide 3-kinase/ protein kinase B… More >

  • Open Access

    ARTICLE

    Profilin 2 Promotes Proliferation and Metastasis of Head and Neck Cancer Cells by Regulating PI3K/AKT/b-Catenin Signaling Pathway

    Kecheng Zhou*†1, Jie Chen*†1, Jiayu Wu*†1, Yangxinzi Xu, Qiaoyun Wu*†, Jingjing Yue*†, Yu Song§, Shengcun Li*†, Peng Zhou, Wenzhan Tu*†, Guanhu Yang*†, Songhe Jiang*†

    Oncology Research, Vol.27, No.9, pp. 1079-1088, 2019, DOI:10.3727/096504019X15579146061957

    Abstract Profilin 2 (PFN2) was found to be mainly expressed in neurons and involved in the development of the brain. In recent years, emerging evidence indicated that PFN2 is also significantly upregulated in various cancers including head and neck cancer (HNSC) and influences cancer cell proliferation, migration, and invasion. However, the role of PFN2 in HNSC development and progression remains unclear. The aim of our study was to investigate the role of PFN2 in the development of HNSC and its possible molecular mechanisms. Bioinformatics showed that increased expression of PFN2 in tumors correlated highly with poor prognosis of HNSC patients. Our… More >

  • Open Access

    ARTICLE

    CRISPR/Cas9-Mediated Gene Knockout of ARID1A Promotes Primary Progesterone Resistance by Downregulating Progesterone Receptor B in Endometrial Cancer Cells

    Haizhen Wang*, Zhenghua Tang*, Ting Li*, Menglu Liu*, Yong Li, Baoling Xing*

    Oncology Research, Vol.27, No.9, pp. 1051-1060, 2019, DOI:10.3727/096504019X15561873320465

    Abstract Medroxyprogesterone (MPA) is used for the conservative treatment of endometrial cancer. Unfortunately, progesterone resistance seriously affects its therapeutic effect. The purpose of the current study was to investigate the influence of deletion of AT-rich interactive domain 1A (ARID1A) in progesterone resistance in Ishikawa cells. Ablation of ARID1A was conducted through the CRISPR/Cas9 technology. Acquired progesterone-resistant Ishikawa (Ishikawa-PR) cells were generated by chronic exposure of Ishikawa cells to MPA. The sensitivity of the parental Ishikawa, Ishikawa-PR, and ARID1A-deficient cells to MPA and/or LY294002 was determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. In addition, Western blot analysis… More >

  • Open Access

    ARTICLE

    Nutlin-3-Induced Sensitization of Non-Small Cell Lung Cancer Stem Cells to Axitinib-Induced Apoptosis Through Repression of Akt1/Wnt Signaling

    Meng Wang*1, Xin Wang†1, Yuan Li‡1, Qiang Xiao§, Xiao-Hai Cui*, Guo-Dong Xiao*, Ji-Chang Wang, Chong-Wen Xu#, Hong Ren*, Dapeng Liu*

    Oncology Research, Vol.27, No.9, pp. 987-995, 2019, DOI:10.3727/096504018X15424918479652

    Abstract The aim of this study was to investigate the potential biological activities of nutlin-3 in the regulation of growth and proliferation of non-small cell lung cancer (NSCLC) stem cells (CSCs), which may help in sensitizing to axitinib-induced apoptosis. Nutlin-3 induction of p53 expression was used to test its role in controlling the cell division pattern and apoptosis of NSCLC cells. A549 cells and H460 cells were pretreated with nutlin-3 and then treated with either an Akt1 activator or shRNA-GSK3 , to investigate the potential role of p53 sensitization in the biological effects of axitinib. We also determined the expression levels… More >

  • Open Access

    ARTICLE

    PD-L1 Induces Epithelial–Mesenchymal Transition in Nasopharyngeal Carcinoma Cells Through Activation of the PI3K/AKT Pathway

    Zhenghua Fei*1, Zhenxiang Deng†1, Lingyang Zhou, Kejie Li*, Xiaofang Xia*, Raoying Xie*

    Oncology Research, Vol.27, No.7, pp. 801-807, 2019, DOI:10.3727/096504018X15446984186056

    Abstract Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma of the head and neck. Cancer therapy targeting programmed cell death protein-1 (PD-1) or programmed death ligand-1 (PD-L1) is revolutionary. However, the tumorigenic mechanism of PD-L1 is not yet clear in NPC. Here we demonstrated an oncogenic role of PD-L1 via activating PI3K/AKT in NPC cells. PD-L1 overexpression was frequently detected in NPC biopsies and cell lines by qRT-PCR. PD-L1 overexpression and knockdown demonstrated that PD-L1 promoted NPC cell invasion and metastasis in vitro and in vivo. Mechanistically, PD-L1 prominently activated the epithelial–mesenchymal transition (EMT) process in a PI3K/AKT-dependent manner. Taken together,… More >

  • Open Access

    ARTICLE

    MicroRNA-101 Targets CXCL12-Mediated Akt and Snail Signaling Pathways to Inhibit Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma

    Fang Chen*, Dongqiang Yang, Yuhua Ru, Shan Cao*, Aishe Gao*

    Oncology Research, Vol.27, No.6, pp. 691-701, 2019, DOI:10.3727/096504018X15426763753594

    Abstract Escalating evidence suggests that microRNA-101 (miR-101) is implicated in the development and progression of various cancers, including papillary thyroid carcinoma (PTC). However, the biological function and molecular mechanisms of miR-101 in PTC are still unclear. In this study, we demonstrated that miR-101 expression was significantly decreased in PTC tissues and cell lines. Clinically, a low level of miR-101 was positively associated with advanced histological stages and lymph node and distant metastases. The expression of CXCL12 was negatively correlated with miR-101 level in PTC. CXCL12 was validated as a direct target of miR-101 in PTC cells. Functional experiments proved that miR-101… More >

  • Open Access

    ARTICLE

    Silencing of NADPH Oxidase 4 Attenuates Hypoxia Resistance in Neuroblastoma Cells SH-SY5Y by Inhibiting PI3K/Akt-Dependent Glycolysis

    Ting Yu*1, Lei Li†1, Wenyan Liu*, Bailiu Ya*, Hongju Cheng*, Qing Xin*

    Oncology Research, Vol.27, No.5, pp. 525-532, 2019, DOI:10.3727/096504018X15179668157803

    Abstract Hypoxia-induced chemoresistance is a major obstacle in the development of effective cancer therapy. In our study, the reversal abilities of NADPH oxidase 4 (NOX4) silence on hypoxia resistance and the potential mechanism were investigated. Our data showed that the expression of NOX4 was upregulated in human neuroblastoma cells SH-SY5Y under hypoxia condition time dependently. Knockdown of NOX4 expression by siRNA inhibited glycolysis induced by hypoxia through decreasing the expression of glycolysis-related proteins (HIF-1 , LDHA, and PDK1), decreasing glucose uptake, lactate production, and ROS production, while increasing mitochondria membrane potential. Moreover, NOX4 silence inhibited cell growth under hypoxia condition through… More >

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