Lung cancer is the leading cause of cancer-related deaths worldwide, characterized by high incidence and mortality rates. The primary reasons for treatment failure in lung cancer patients are tumor invasion and drug resistance, particularly resistance to chemotherapeutic agents and epidermal growth factor receptor (EGFR) mutant targeted therapy, which considerably undermine the therapeutic outcomes for those with advanced lung cancer. Epithelial-mesenchymal transition (EMT) serves as a crucial biological process closely associated with physiological or pathological processes such as tissue embryogenesis, organogenesis, wound repair, and tumor invasion. Numerous studies have indicated that EMT, mediated through various signaling pathways, plays a pivotal role in the initiation, progression, and metastasis of lung cancer, while it is also closely associated with drug resistance in lung cancer cells. Therefore, research focusing on the molecular mechanisms and pathophysiology related to EMT can contribute to reversing drug resistance in drug treatment for lung cancer, thereby improving prognosis. This article reviews the progress in research on EMT in the invasion, metastasis, and drug resistance of lung cancer based on relevant domestic and international literature.
Humans ; Epithelial-Mesenchymal Transition/drug effects* ; Drug Resistance, Neoplasm ; Lung Neoplasms/physiopathology* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Animals ; Antineoplastic Agents/therapeutic use*

BACKGROUND: Abnormalities of the switch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex are closely related to various cancers, and ARID1B (AT-rich interaction domain 1B) is one of the core subunits of the SWI/SNF complex. Mutations or copy number deletions of the ARID1B gene are associated with impaired DNA damage response and altered chromatin accessibility. However, whether ARID1B deficiency affects the proliferation, migration and invasion abilities of non-small cell lung cancer (NSCLC) cells and its molecular mechanisms remain poorly understood. This study aims to reveal the regulatory role of ARID1B gene deletion on the malignant phenotype of NSCLC cells and its molecular mechanism. METHODS: Online databases were used to analyze the relationship between ARID1B and the prognosis of patients with lung cancer, and the expression levels of ARID1B in lung cancer tissues. The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat) technology was employed to construct stable ARID1B gene knockout (KO) cell lines. The plate colony formation assay was used to detect cell proliferation, and the Transwell cell migration and invasion assays were used to detect changes in cell migration ability. RNA-Seq was utilized for the expression and enrichment analysis of differentially expressed genes. Western blot (WB) was used to verify the knockout effect of the ARID1B gene and to detect the expression changes of epithelial-mesenchymal transition (EMT) markers and mitogen-activated protein kinases (MAPK) signaling pathway-related proteins. Nude mouse tumor models were constructed and the tumorigenic abilities of control and ARID1B-deficient cells were compared. RESULTS: Patients with low ARID1B expression have poor overall survival. ARID1B is differentially expressed in lung cancer and normal tissues, and its expression level being lower in cancer cells. ARID1B-deficient cells had significantly enhanced in vitro proliferation, migration and invasion abilities. In animal experiments, the tumor formation speed of ARID1B gene deficient cells was significantly accelerated. Enrichment analysis of RNA-Seq results revealed that the differentially expressed genes were mainly enriched in MAPK, phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) and other signaling pathways. WB experiments demonstrated that the expressions of E-cadherin, N-cadherin and Vimentin changed in ARID1B gene deficient cells, and the expressions of MAPK and p-MAPK was increased. CONCLUSIONS The A549-ARID1B KO and PC9-ARID1B KO cell lines were successfully established. The ARID1B-deficient cell lines demonstrated high migration, invasion and proliferation potential at both in vitro and in vivo biological behavior levels and at the transcriptome sequencing level. The changes in the expression of EMT markers and the activation of the MAPK signaling pathway suggest possible metastasis mechanisms of ARID1B-deficient NSCLC.
Humans ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Lung Neoplasms/metabolism* ; Animals ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Transcription Factors/metabolism* ; Neoplasm Invasiveness ; Mice ; DNA-Binding Proteins/metabolism* ; Gene Deletion ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Mice, Nude ; Gene Expression Regulation, Neoplastic

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy is the primary surgical treatment for lung cancer. A significant factor affecting postoperative recovery is prolonged air leak (PAL). Despite numerous clinical strategies could prevent and manage postoperative PAL, its incidence remains high. Phrenic nerve cryotherapy (PNC) temporarily inhibits phrenic nerve function, causing diaphragm elevation, which reduces thoracic cavity volume, enhances pleural apposition, and mitigates air leakage. This study investigates the efficacy of PNC in preventing postoperative PAL during VATS lobectomy. METHODS: A total of 108 eligible lung cancer patients who underwent surgery at the Department of Thoracic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, from June 2023 to January 2025, were enrolled and randomly assigned to the control group (n=54) and the experimental group (n=54). The patients in both the two groups received VATS lobectomy and systematic lymph node dissection, with the experimental group also undergoing PNC during the operation. The baseline characteristics, intraoperative, postoperative indicators and dynamic changes in air leakage between the two groups were compared. RESULTS: The baseline clinical characteristics were comparable between the two groups (P>0.05). The incidence of pulmonary air leakage at 24 h after surgery (31.5% vs 29.6%) and the incidence of postoperative PAL (20.4% vs 14.8%) showed no significant differences between the two groups (P>0.05). The intraoperative air leak test to 24 hours after surgery revealed that air leakage ceased in 8 cases (32.0%) in the control group, compared to 14 cases (46.7%) in the experimental group. Moreover, during the progression from air leakage at 24 hours post-surgery to postoperative PAL, air leakage ceased in 6 cases (35.3%) in the control group and 8 cases (50.0%) in the experimental group, with a statistically significant difference (P<0.001). Compared to the control group, the patients in the experimental group exhibited more pronounced postoperative diaphragmatic elevation that recovered to a slightly higher than preoperative level by 3 mon after surgery. CONCLUSIONS The combination of PNC and active lung repair can serve as an important intervention for patients at high risk of intraoperative air leakage, reducing the occurrence of postoperative PAL.
Humans ; Thoracic Surgery, Video-Assisted/adverse effects* ; Male ; Female ; Middle Aged ; Lung Neoplasms/surgery* ; Aged ; Phrenic Nerve/physiopathology* ; Cryotherapy ; Pneumonectomy/adverse effects* ; Postoperative Complications/etiology* ; Adult

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

The study investigated the effect of casticin on the proliferation of non-small cell lung cancer(NSCLC) H322 cells and explored its molecular mechanism. Firstly, the cell counting kit-8(CCK-8) assay, colony formation assay, and EdU assay were used to detect the effect of casticin on the proliferation capacity of H322 cells under different concentrations and treatment durations. Then, glucose uptake, lactate production, extracellular pH, and oxygen consumption of H322 cells were measured before and after casticin treatment to analyze its impact on glycolysis in NSCLC H322 cells. Finally, real-time fluorescence quantitative PCR(RT-qPCR) and Western blot assays were performed to explore glycolysis-related molecules affected by casticin. The experiments showed that casticin inhibited the proliferation of NSCLC H322 cells in a dose-and time-dependent manner, with half-maximal inhibitory concentrations(IC_(50)) of 28.64 and 19.41 μmol·L~(-1) after 48 and 72 hours of treatment, respectively. Casticin also inhibited glucose uptake and lactate production in H322 cells, while increasing extracellular pH and oxygen consumption. Further investigation revealed that casticin inhibited the expression of glycolysis-related molecules, including glucose transporter 1(GLUT1), hexokinase 2(HK2), aldolase A(ALDOA), pyruvate kinase M2(PKM2), and hypoxia-inducible factor-1α(HIF-1α). Overexpression of HIF-1α was found to reverse the inhibitory effects of casticin on H322 cell proliferation and glycolysis. These findings suggest that casticin may regulate cellular glycolysis by inhibiting the expression of HIF-1α, thereby inhibiting the proliferation of NSCLC H322 cells. This study identifies a potential drug for the treatment of NSCLC and provides a direction for further research.
Humans ; Cell Proliferation/drug effects* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Lung Neoplasms/drug therapy* ; Glucose/metabolism* ; Cell Line, Tumor ; Glycolysis/drug effects*

Immune cell infiltration is of great significance for the diagnosis and prognosis of cancer. In this study, we collected gene expression data of non-small cell lung cancer (NSCLC) and normal tissues included in TCGA database, obtained the proportion of 22 immune cells by CIBERSORT tool, and then evaluated the infiltration of immune cells. Subsequently, based on the proportion of 22 immune cells, a classification model of NSCLC tissues and normal tissues was constructed using machine learning methods. The AUC, sensitivity and specificity of classification model built by random forest algorithm reached 0.987, 0.98 and 0.84, respectively. In addition, the AUC, sensitivity and specificity of classification model of lung adenocarcinoma and lung squamous carcinoma tissues constructed by random forest method 0.827, 0.75 and 0.77, respectively. Finally, we constructed a prognosis model of NSCLC by combining the immunocyte score composed of 8 strongly correlated features of 22 immunocyte features screened by LASSO regression with clinical features. After evaluation and verification, C-index reached 0.71 and the calibration curves of three years and five years were well fitted in the prognosis model, which could accurately predict the degree of prognostic risk. This study aims to provide a new strategy for the diagnosis and prognosis of NSCLC based on the classification model and prognosis model established by immune cell infiltration.
Algorithms ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; physiopathology ; Humans ; Lung Neoplasms ; diagnosis ; physiopathology ; Machine Learning ; Prognosis

In recent years, the incidence and detection rate of lung cancer have gradually increased, and segmentectomy has been increasingly used to treat early non-small cell lung cancer. Some scholars believe that segmentectomy is more conducive to the preservation of postoperative lung function than lobectomy. Some studies have found that the two surgical methods have little difference in postoperative cost retention. This article deals with segmentectomy and lobectomy. A review of related studies on postoperative pulmonary function changes.
.
Humans ; Lung ; physiopathology ; surgery ; Lung Neoplasms ; physiopathology ; surgery ; Pneumonectomy ; adverse effects ; methods ; Recovery of Function

As the core of cellular immunotherapy, T cells are important aspects of research and treatment of lung cancer. IL-6 is a costimulatory signal factor of T cells that is directly targeted by lung cancer stem cells. As a highly expressed cytokine in lung cancer cells, IL-6 plays an important role in variety of biological activities such as tumor occurrence, development, invasion and metastasis. This article reviews the research progress on IL-6 in lung cancer, including cancer development and progression, and the therapeutic sensitivity of lung cancer.
Disease Progression ; Humans ; Interleukin-6 ; metabolism ; Lung Neoplasms ; physiopathology ; Neoplastic Stem Cells ; pathology ; Research ; trends ; T-Lymphocytes ; metabolism

OBJECTIVEEscape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe.

METHODSAn orthotopic transplant model of mouse Lewis lung cancer, with stable expression of IDO gene, was established in C57BL/6 mice. Optical imaging was used to observe the effects of Feiji Recipe in the treatment of lung cancer in vivo. The effects of Feiji Recipe on the proliferation of mouse Lewis lung cancer cell line 2LL, 2LL-enhanced green fluorescent protein (2LL-EGFP) and 2LL-EGFP-IDO were investigated, and the apoptosis of T-cells was examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide using flow cytometry. Chemical composition of Feiji Recipe was validated by high-performance liquid chromatography.

RESULTSCompared to the control group, the survival of animals treated with Feiji Recipe was significantly prolonged (P = 0.0074), and the IDO protein level decreased (P = 0.0072); moreover, the percentages of CD4CD25 T-cells and Foxp3 T-cells were significantly decreased (P < 0.05). The molecular mechanism of Feiji Recipe against lung cancer may relate to the regulation of immune cells, such as T-cells and regulatory T-cells.

CONCLUSIONThe molecular mechanism of Feiji Recipe in treatment of lung cancer is to restore the function of T-cells in the cancer microenvironment through interfering with the IDO pathway.

Animals ; Apoptosis ; drug effects ; Carcinoma, Lewis Lung ; drug therapy ; enzymology ; immunology ; physiopathology ; Cell Proliferation ; drug effects ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Growth Inhibitors ; administration & dosage ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; genetics ; immunology ; Lung Neoplasms ; drug therapy ; enzymology ; immunology ; physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; drug effects ; immunology

BACKGROUND: Angiogenesis is an important process in the development of tumor. PD 0332991, a cell cycle inhibitor, can specifically inhibit CD4/6 phosphorylation and cell cycle progression. In xeongraft mice models, PD 0332991 treated mice had significantly decreased angiogenesis and vascular density compared with the control group, but the mechanism remains unknown. The purpose of this study is to investigate the role and molecular mechanism of PD 0332991 on vascular endothelial cells. METHODS: EA.hy926 cells, a kind of vascular endothelial cell, were used as the research model. The effects of PD 0332991 on the activity and proliferation of EA.hy926 cells were detected by the MTT, EdU assays. Wound-healing assays and transwell assays were used to determine the effects of PD 0332991 on the mobility of EA.hy926. The influence of PD 0332991 on cell cycle and apoptosis of endothelial cells was tested by flow cytometry, and the Western blot was applied to observe the expression of cell cycle related proteins in EA.hy926 cells treated by PD 0332991. RESULTS: PD 0332991 significantly inhibited the proliferation and mobility of EA.hy926 cells, caused cell cycle arrest and apoptosis. At the same time, PD 0332991 inhibited the expression of CDK4/6 and phosphorylation of Rb, and thus inhibited the cell cycle progression of EA.hy926 cells. CONCLUSIONS PD 0332991 can inhibit the proliferation and activity of endothelial cells and induces apoptosis.
Angiogenesis Inhibitors ; pharmacology ; Animals ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cyclin-Dependent Kinase 4 ; genetics ; metabolism ; Cyclin-Dependent Kinase 6 ; genetics ; metabolism ; Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Lung Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Mice ; Piperazines ; pharmacology ; Pyridines ; pharmacology