• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1391-1396
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• 2014

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the most common cause of lung cancer death. Currently, the epidermal growth factor receptor inhibitor gefitinib is used for its treatment; however, drug resistance is a major obstacle. Expression of Met has been associated with both primary and acquired resistance to gefitinib, but the mechanisms regulating its expression are not fully understood. Recently, miRNAs such as miR-130a have been shown to play a role in gefitinib resistance, but importance in NSCLC and relationships with Met have not been fully explored. Here we show that miR-130a is over-expressed in gefitinibsensitive NSCLC cell lines, but is low in gefitinib-resistant NSCLC cell lines. Moreover, miR-130a expression was negatively correlated with that of Met. Further analysis revealed that over-expression of miR-130a increased cell apoptosis and inhibited proliferation of NSCLC cells treated with gefitinib, whereas lowering the expression of miR-130a decreased cell apoptosis and promoted cell proliferation after treatment with gefitinib in both gefitinib-sensitive and -resistant NSCLC cell lines, suggesting that miR-130a overcomes gefitinib resistance. We also demonstrated that miR-130a binds to the 3'-UTR of Met and significantly suppresses its expression. Finally, our results showed that over-expressing Met could "rescue" the functions of miR-130a regarding cell apoptosis and proliferation after cells are treated with gefitinib. These findings indicate that the miR-130a/Met axis plays an important role in gefitinib resistance in NSCLC. Thus, the miR-130a/Met axis may be an effective therapeutic target in gefitinib-resistant lung cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.2355-2362
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• 2012

The SH2B1 adaptor protein is recruited to multiple ligand-activated receptor tyrosine kinases that play important role in the physiologic and pathologic features of many cancers. The purpose of this study was to assess SH2B1 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Methods: SH2B1 expression in 114 primary NSCLC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Additionally, 15 paired NSCLC background tissues, 5 NSCLC cell lines and a normal HBE cell line were evaluated for SH2B1 expression by RT-PCR and immunoblotting, immunofluorescence being applied for the cell lines. Results: SH2B1 was found to be overexpressed in NSCLC tissues and NSCLC cell lines. More importantly, high SH2B1 expression was significantly associated with tumor grade, tumor size, clinical stage, lymph node metastasis, and recurrence respectively. Survival analysis demonstrated that patients with high SH2B1 expression had both poorer disease-free survival and overall survival than other patients. Multivariate Cox regression analysis revealed that SH2B1 overexpression was an independent prognostic factor for patients with NSCLC. Conclusions: Our findings suggest that the SH2B1 protein may contribute to the malignant progression of NSCLC and could offer a novel prognostic indicator for patients with NSCLC.

• Journal of Nutrition and Health
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• 제56권1호
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• pp.12-23
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• 2023

Purpose: This study investigates the alterations in A549 human non-small-cell lung cancer (NSCLC) cells exposed to Citrus junos extract (CJE). We further examine the antiproliferative and apoptotic effects of CJE on NSCLC cells. Methods: Inhibition of proliferation was examined by applying the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) colorimetric assay on CJE-treated A549 NSCLC cells. The lactate dehydrogenase (LDH) assay was performed to measure the degree of toxicity of CJE on NSCLC cells. The effect on migratory proliferation was confirmed using the scratch wound healing assay. The antiproliferative effect of the CJE on human lung cancer cells was verified through morphological observation, fluorescence microscopy, and caspase-3 colorimetry. Results: Exposure of NSCLC cells to CJE resulted in a dose- and time-dependent decrease in cell activity and increased toxicity to the cells. In addition, microscopic observation revealed a reduced ability of the cancer cells to migrate and proliferate after exposure to the CJE, with simultaneous morphological apoptotic changes. Fluorescence staining and microscopic examination revealed that this death was a process of self-programmed cell death of NSCLC cells. Compared to unexposed NSCLC cells, the expression of caspase-3 was significantly increased in cells exposed to CJE. Conclusion: Exposure of A549 human NSCLC cells to CJE inhibits the proliferation, increases the cytotoxicity, and decreases the ability of cells to migrate and grow. Moreover, the expression of caspase-3 increases after CJE treatment, suggesting that the apoptosis of NSCLC cells is induced by a chain reaction initiated by caspase-3. These results indicate that Citrus junos is a potential therapeutic agent for human non-small-cell lung cancer.

• 대한약침학회지
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• 제21권4호
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• pp.268-276
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• 2018

Objectives: The purpose of this study is to investigate the anti-cancer effects of different fractions of Astragalus membranaceus (AM) in human non-small cell lung cancer (NSCLC) cells. Methods: We isolated hexane, ethyl acetate, and butanol fractions from crude ethanol extract of AM. The cell death was examined by MTT assay and trypan blue exclusion assay. Apoptosis was detected by DAPI staining, annexin V-PI double staining and cell cycle analysis. The expression of apoptosis-related proteins and mitogen-activated protein kinases (MAPKs) was examined by western blot. Results: Among various fractions of AM, the ethyl acetate fraction of AM (EAM) showed the strongest cytotoxic effect in NSCLC cells. EAM reduced the cell proliferation in a time- and dose-dependent manner in NSCLC cells. In addition, EAM induced the chromatin condensation, and increased the population of sub-G1 phase and annexin V-positive cells in a time-dependent manner, indicating that EAM induced apoptosis in NSCLC cells. Consistently, EAM enhanced the expression of cleaved caspase-8 and -9, and induced the accumulation of cleaved- poly (ADP-ribose) polymerase (PARP). Among MAPK proteins, only ERK was dephosphorylated by EAM, suggesting that ERK might be related with EAM-induced apoptosis. Conclusion: Our results clearly demonstrate that EAM exhibited anti-cancer effects in NSCLC cells by induction of apoptosis. We provide a valuable evidence which suggests that AM could be a desirable therapeutic option for treatment of NSCLC.

• Journal of Ginseng Research
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• 제47권2호
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• pp.291-301
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• 2023

Introduction: Non-small cell lung cancer (NSCLC) patients are particularly vulnerable to the Coronavirus Disease-2019 (COVID-19). Currently, no anti-NSCLC/COVID-19 treatment options are available. As ginsenoside Rg3 is beneficial to NSCLC patients and has been identified as an entry inhibitor of the virus, this study aims to explore underlying pharmacological mechanisms of ginsenoside Rg3 for the treatment of NSCLC patients with COVID-19. Methods: Based on a large-scale data mining and systemic biological analysis, this study investigated target genes, biological processes, pharmacological mechanisms, and underlying immune implications of ginsenoside Rg3 for NSCLC patients with COVID-19. Results: An important gene set containing 26 target genes was built. Target genes with significant prognostic value were identified, including baculoviral IAP repeat containing 5 (BIRC5), carbonic anhydrase 9 (CA9), endothelin receptor type B (EDNRB), glucagon receptor (GCGR), interleukin 2 (IL2), peptidyl arginine deiminase 4 (PADI4), and solute carrier organic anion transporter family member 1B1 (SLCO1B1). The expression of target genes was significantly correlated with the infiltration level of macrophages, eosinophils, natural killer cells, and T lymphocytes. Ginsenoside Rg3 may benefit NSCLC patients with COVID-19 by regulating signaling pathways primarily involved in anti-inflammation, immunomodulation, cell cycle, cell fate, carcinogenesis, and hemodynamics. Conclusions: This study provided a comprehensive strategy for drug discovery in NSCLC and COVID-19 based on systemic biology approaches. Ginsenoside Rg3 may be a prospective drug for NSCLC patients with COVID-19. Future studies are needed to determine the value of ginsenoside Rg3 for NSCLC patients with COVID-19.

• Nuclear Medicine and Molecular Imaging
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• 제42권sup1호
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• pp.17-28
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• 2008

This review focuses on the clinical use of $^{18}F-FDG$ PET to evaluate solitary pulmonary nodule (SPN) and non-small cell lung cancer (NSCLC). When SPN or mass without calcification is found on chest X-ray or CT, $^{18}F-FDG$ PET is an effective modality to differentiate benign from malignant lesions. For initial staging of NSCLC, $^{18}F-FDG$ PET is useful, and proved to be cost-effective in several countries. $^{18}F-FDG$ is useful for detecting recurrence, restaging and evaluating residual tumor after curative therapy in NSCLC. For therapy response assessment, $^{18}F-FDG$ PET may be effective after chemotherapy or radiation therapy. $^{18}F-FDG$ PET is useful to predict pathological response after neoadjuvant therapy in NSCLC. For radiation therapy planning, $^{18}F-FDG$ PET may be helpful, but requires further investigations. PET/CT is better for evaluating NSCLC than conventional PET.

• 생명과학회지
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• 제29권6호
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• pp.645-652
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• 2019

전세계적으로 폐암 발병율은 서서히 감소하는 추세이지만, 여전히 암 관련 사망의 주요 원인으로 지목되고 있으며, 이에 따라 폐암 진단과 치료를 위한 새로운 분자적 지표를 발굴하는 연구가 활발히 이루어지고 있다. 본 연구진이 수행한 기존 연구에 따르면 폐암 환자에게서는 전사인자 중 하나인 TFAP2C가 높은 비율로 발현되며, 이 전사인자를 통해 폐암 발달에 상당한 영향을 끼치는 것을 확인할 수 있었다. TFAP2C는 다른 유전자들의 발현을 조절하여 암 형성에 기여하게 된다. 마이크로어레이 분석을 통해 TFAP2C에 의해 발현양이 조절되는 잠재적 표적 유전자들을 확인하였고, 특히 TFAP2C siRNA를 처리하였을 때 발현이 감소되는 원암유전자들 중 CDC20과 TRIB3 유전자를 최종적으로 선별하였다. 리얼타임 qRT-PCR과 웨스턴블롯을 통하여 두 유전자가 TFAP2C에 의존적으로 발현됨을 확인하였으며, 세포 생존 분석법을 통하여 CDC20과 TRIB3의 발현 증가가 폐암세포의 세포 증식을 유의미하게 유도하는 것을 확인하였다. 이와 더불어, CDC20과 TRIB3의 과발현이 폐암세포의 세포사멸 수준을 감소시켜 폐암 형성에 관여함을 확인하였다. 본 연구를 통하여 CDC20과 TRIB3가 폐암 형성을 유도할 수 있는 잠재적인 원암유전자로 기능함을 밝힐 수 있었으며, 두 유전자가 폐암 진단을 위한 표적유전자로서의 역할을 수행할 수 있을 것으로 기대한다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2563-2566
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• 2013

Background: Interleukin-33 (IL-33) has recently been implicated in tumor immunity. The aim of this study was to explore the clinical role of serum IL-33 in patients with non-small-cell lung cancer (NSCLC). Methods: Sera collected from 250 healthy volunteers (HV), 256 patients with benign lung diseases (BLD) and 262 NSCLC cases were subjected to IL-33 ELISA and relationships between serum IL-33 and clinical characteristics were evaluated. Results: Circulating IL-33 levels were higher in the NSCLC group in comparison with the HV and BLD groups (p<0.001). Using a cut-off level 68 pg/ml (95% specificity in the HV group), IL-33 showed a good diagnostic performance for NSCLC. Multivariate survival analysis indicated that serum IL-33 was an independent prognostic factor in the entire NSCLC group [hazards ratio (HR) = 0.64 for low versus high IL-33 levels, 95% confidence interval (CI) 0.50-0.82; p<0.001] and in 165 selected patients with locally advanced or metastatic disease receiving chemoradiotherapy or chemotherapy (HR 0.70, 95% CI 0.52-0.94; p=0.013). Conclusions: IL-33 is a promising potential diagnostic and prognostic marker in NSCLC, independent of the therapeutic intervention.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3725-3728
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• 2013

Background: The mammalian target of rapamycin (mTOR) /RPS6KB1 activation has recently been implicated in tumour development, but its role in lung cancer remains unclear. The aim of this study was to explore the role of mTOR/RPS6KB1 signaling pathway in non-small-cell lung cancer (NSCLC). Methods: Immunohistochemistry was performed to assess the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and its downstream ribosomal phosphorylated RPS6KB1 (p-RPS6KB1) in NSCLC patients. We also analyzed p-mTOR/p-RPS6KB1 protein expression in 45 fresh NSCLC tissues using Western blotting. Results: The expression level of p-mTOR and p-RPS6KB1 was significantly higher in NSCLC tumor specimens than that in adjacent noncancerous normal lung tissues (P<0.01). p-mTOR expression correlated with p-RPS6KB1. Furthermore, high expression level of p-mTOR or p-RPS6KB1 in NSCLC was associated with a shorter overall survival (both P<0.01). Multivariate analysis indicated high level of p-mTOR expression was an independent prognostic factor (HR=2.642, 95%CI 1.157-4.904, p=0.002). Conclusions: p-mTOR and p-RPS6KB1 could be useful prognostic markers for NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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• pp.4671-4673
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• 2013

Objectives: To study variation in T lymphocyte subgoups and its clinical significance in non-small cell lung cancer (NSCLC). Methods: Levels of CD3+, CD4+, CD8+, CD4+/CD8+, NK and Treg cells in peripheral blood of NSCLC cases and healthy adults were determined by flow cytometry. Results: CD3+, CD4+ and CD4+/CD8+ ratio and NK cells in NSCLCs were decreased significantly in comparison with the control group (P < 0.01), and decreased with increase in the clinical stage of NSCLC, while CD8+ cells demonstrated no significant change (P > 0.05). Treg cells were significantly more frequent than in the control group (P < 0.01), and increased with the clinical stage of NSCLC. Conclusion: The cellular immune function of the NSCLC patients is lowered. It is important to detect change of T lymphocyte subgroups by flow cytometry for the diagnosis, treatment and prognostic assessment of NSCLC patients.