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Docetaxel and Gemcitabine Modulate Cellular Effects and Long Non-Coding RNA Profiles in Non-Small Cell Lung Cancer
Andrei-Alexandru Tirpe1, Lajos Raduly1, Oana Zanoaga1
1Department of Genomics, MEDFUTURE Institute for Biomedical Research, Iuliu Hațieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania.
Abstract:
Lung cancer remains the most prevalent and deadliest malignancy worldwide. According to the European Society for Medical Oncology guidelines for non-oncogene-addicted metastatic non-small-cell lung cancer (NSCLC), patients with metastatic squamous-cell carcinoma (LUSC) or metastatic non-squamous NSCLC with performance status 2 and PD-L1 < 50% may receive single-agent chemotherapy with gemcitabine (GEM), docetaxel (DOC), or vinorelbine. Herein, we investigated the cellular effects of GEM/DOC as monotherapies in NSCLC cell lines-lung adenocarcinoma, A549 and CALU6; LUSC, H520 and H1703. Treatment with GEM/DOC may induce apoptotic cell death in all NSCLC cell lines at 48 h. GEM/DOC can affect cancer cell migration assessed by scratch assay. Both GEM/DOC may produce distinct effects on cell cycle arrest, consistent with their particular pharmacodynamic effects. Furthermore, GEM/DOC induced signals consistent with autophagic activity in LUSC cell lines, but only GEM triggered signals consistent with autophagic activity in the CALU6 cell line. Analysis of three key long non-coding RNAs (lncRNAs)-MALAT1, NEAT1, and HOTAIR-showed variable expression in the studied cell lines as a potential response to DOC and GEM treatment. Our findings indicate different cellular effects of GEM and DOC in NSCLC cell lines and provide an overview of how currently used chemotherapeutics may influence the expression of lncRNAs.
Insights
Gemcitabine (GEM) and docetaxel (DOC) chemotherapy can induce cell death and affect migration in non-small cell lung cancer (NSCLC) cell lines. These agents also impact cell cycle, autophagy, and long non-coding RNA expression in lung cancer models.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Lung cancer is a leading cause of cancer-related mortality globally.
- Current guidelines suggest gemcitabine (GEM) or docetaxel (DOC) monotherapy for specific non-small cell lung cancer (NSCLC) patient groups.
- Understanding the cellular mechanisms of these chemotherapeutics is crucial for optimizing treatment.
Purpose of the Study:
- To investigate the distinct cellular effects of GEM and DOC as monotherapies in various NSCLC cell lines.
- To analyze the impact of GEM and DOC on apoptosis, migration, cell cycle, autophagy, and long non-coding RNA (lncRNA) expression.
- To provide insights into the pharmacodynamic actions of GEM and DOC in NSCLC.
Main Methods:
- Utilized NSCLC cell lines including lung adenocarcinoma (A549, CALU6) and lung squamous cell carcinoma (LUSC, H520, H1703).
- Assessed cellular effects including apoptotic cell death, cell migration (scratch assay), cell cycle arrest, and autophagic activity.
- Analyzed the expression of key lncRNAs (MALAT1, NEAT1, HOTAIR) in response to GEM and DOC treatment.
Main Results:
- GEM and DOC induced apoptotic cell death in all tested NSCLC cell lines within 48 hours.
- Both chemotherapeutics affected cancer cell migration and induced distinct cell cycle arrest patterns.
- GEM and DOC triggered autophagic signals in LUSC lines, with GEM also showing effects in CALU6.
- Variable expression of MALAT1, NEAT1, and HOTAIR was observed in response to GEM and DOC.
Conclusions:
- GEM and DOC exhibit differential cellular effects in NSCLC models.
- These chemotherapeutics influence fundamental cancer processes like apoptosis, migration, and cell cycle progression.
- The study highlights the potential of GEM and DOC to modulate lncRNA expression, suggesting novel therapeutic avenues.
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