Abstract
Background: Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients.
Objective: Establishment of the OSI-resistant HCC827/OSIR cell line and study of its resistant mechanism.
Method: The anti-proliferative effect was studied through MTT and colony formation assays. The protein expression was detected by Western blot assay. The gene was silenced by small interfering RNA. The cellular morphology was observed by using an optical microscope. The viable cell numbers were counted by trypan blue staining assay.
Results: The OSI-resistant HCC827/OSIR cells were established on HCC827 cells with naive EGFR-sensitive mutation, and the resistant effects of HCC827/OSIR cells were confirmed through MTT and colony formation assays. The IC50s of HCC827/OSIR cells to other EGFR TKIs, such as gefitinib, erlotinib, afatinib, and rociletinib was higher than that of the HCC827 cells. The anti-proliferative effects of paclitaxel, pemetrexed, doxorubicin, and fluorouracil in HCC827 and HCC827/OSIR cells were similar. The expression of inositolrequiring enzyme 1α (IRE1α) was increased after the cells developed resistance to OSI. The number of viable cells in both cell lines, particularly in HCC827/OSIR cells, was decreased through knockdown of IRE1α or pretreatment with STF-083010, an IRE1α inhibitor.
Conclusion: An increased expression of IRE1α may be one of the resistant mechanisms for OSI-resistant NSCLC.
Keywords: Osimertinib, AZD9291, EGFR, IRE1α, NSCLC, lune cancer.
Anti-Cancer Agents in Medicinal Chemistry
Title:Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells
Volume: 18 Issue: 4
Author(s): Zheng-hai Tang, Min-Xia Su, Xia Guo, Xiao-Ming Jiang, Lin Jia, Xiuping Chen and Jin-Jian Lu*
Affiliation:
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao,China
Keywords: Osimertinib, AZD9291, EGFR, IRE1α, NSCLC, lune cancer.
Abstract: Background: Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients.
Objective: Establishment of the OSI-resistant HCC827/OSIR cell line and study of its resistant mechanism.
Method: The anti-proliferative effect was studied through MTT and colony formation assays. The protein expression was detected by Western blot assay. The gene was silenced by small interfering RNA. The cellular morphology was observed by using an optical microscope. The viable cell numbers were counted by trypan blue staining assay.
Results: The OSI-resistant HCC827/OSIR cells were established on HCC827 cells with naive EGFR-sensitive mutation, and the resistant effects of HCC827/OSIR cells were confirmed through MTT and colony formation assays. The IC50s of HCC827/OSIR cells to other EGFR TKIs, such as gefitinib, erlotinib, afatinib, and rociletinib was higher than that of the HCC827 cells. The anti-proliferative effects of paclitaxel, pemetrexed, doxorubicin, and fluorouracil in HCC827 and HCC827/OSIR cells were similar. The expression of inositolrequiring enzyme 1α (IRE1α) was increased after the cells developed resistance to OSI. The number of viable cells in both cell lines, particularly in HCC827/OSIR cells, was decreased through knockdown of IRE1α or pretreatment with STF-083010, an IRE1α inhibitor.
Conclusion: An increased expression of IRE1α may be one of the resistant mechanisms for OSI-resistant NSCLC.
Export Options
About this article
Cite this article as:
Tang Zheng-hai , Su Min-Xia , Guo Xia , Jiang Xiao-Ming , Jia Lin , Chen Xiuping and Lu Jin-Jian *, Increased Expression of IRE1α Associates with the Resistant Mechanism of Osimertinib (AZD9291)-resistant non-small Cell Lung Cancer HCC827/OSIR Cells, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (4) . https://dx.doi.org/10.2174/1871520617666170719155517
DOI https://dx.doi.org/10.2174/1871520617666170719155517 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Approaches for Developing Novel Microtubule Targeting Agents (MTAs) for Therapeutic Exploitation
Current Pharmaceutical Design Compounds Combining Aminoadamantane and Monoterpene Moieties: Cytotoxicity and Mutagenic Effects
Medicinal Chemistry Treatment of Relapsed Acute Myeloid Leukaemia
Reviews on Recent Clinical Trials Cancer Biomarker Discovery for Precision Medicine: New Progress
Current Medicinal Chemistry Sleep Disturbances in Lung Cancer Patients
Current Respiratory Medicine Reviews Integrins: Novel Therapeutic Targets for Cardiovascular Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Polysialyltransferase: A New Target in Metastatic Cancer
Current Cancer Drug Targets Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells
Anti-Cancer Agents in Medicinal Chemistry Isolation, Characterization and Preliminary Cytotoxic and Antifungal Evaluations of Novel Lancifoliate Isolated from Methanol Extract of <i>Conocarpus lancifolius</i>
Anti-Cancer Agents in Medicinal Chemistry Glioblastoma Multiforme and its Cell Interruption
Current Cancer Therapy Reviews Context-dependent Action of Transforming Growth Factor β Family Members on Normal and Cancer Stem Cells
Current Pharmaceutical Design Recent Progress in the Development of Synthetic Hybrids of Natural or Unnatural Bioactive Compounds for Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry Recent Patents on Thiazole Derivatives Endowed with Antitumor Activity
Recent Patents on Anti-Cancer Drug Discovery n-3 Polyunsaturated Fatty Acids and the Prevention of Colorectal Cancer: Molecular Mechanisms Involved
Current Medicinal Chemistry Circulating Tumor Cells (CTCs) as a Liquid Biopsy Material and Drug Target
Current Drug Targets How Do HIV-Infected Smokers React to Cigarette Price Increases? Evidence from the Aproco-Copilote-ANRS CO8 Cohort
Current HIV Research Role of Glioma-associated GLI1 Oncogene in Carcinogenesis and Cancertargeted Therapy
Current Cancer Drug Targets System Level Meta-analysis of Microarray Datasets for Elucidation of Diabetes Mellitus Pathobiology
Current Genomics Recent Advances in the Analyses of Carotenoids and Their Role in Human Health
Current Pharmaceutical Analysis Targeting Tumor Proteasome with Traditional Chinese Medicine
Current Drug Discovery Technologies