• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2807-2812
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• 2012

The purpose of this study was to examine the effect of a Toll-like receptor 5 (TLR5) agonist, CBLB502, on the growth and radiosensitivity of A549 lung cancer cells in vivo. Expression of myeloid differentiation factor 88 (MyD88) or TLR5 was stably knocked down in human lung cancer cells (A549) using lentivirus expressing short hairpin RNA targeting human MyD88 or TLR5. Lack of MyD88 or TLR5 expression enhanced tumor growth in mouse xenografts of A549 lung cancer cells. CBLB502 inhibited the growth of A549 lung cancer cells, not A549-MyD88-KD cells in vivo in the murine xenograft model. Our results showed that the inhibition of A549 by CBLB502 in vivo was realized through regulating the expression of neutrophil recruiting cytokines and neutrophil infiltration. Finally, we found that activation of TLR5 signaling did not affect the radiosensitivity of tumors in vivo.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4635-4639
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• 2013

Multi-drug resistance (MDR) is an essential aspect of human lung cancer chemotherapy failure. Recent studies have shown that vinorelbine is involved in underlying processes in human tumors, reversing the MDR inseveral types of cancer cells. However, the roles and potential mechanism are not fully clear. In this study, we explored effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549/DDP cells. We found that vinorelbine increased drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase ${\pi}$ (GST-${\pi}$) in A549/DDP cells. At the same time, we also established downregulation of p-Akt and decreased transcriptional activation of NF-${\kappa}B$ and twist after vinorelbine treatment. The results indicated that vinorelbine might be used as a potential therapeutic strategy in human lung cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.1
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• pp.61-66
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• 2014

Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigallocatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3005-3009
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• 2014

The aims of this study were to investigate the influence of ubiquitin- conjugating enzyme E2C (UBE2C) on biological behavior of lung cancer cells. Using MTT, flow cytometry and invasion assays, we detected UBE2C expression and evaluated its biological properties in these cells, including effects on proliferation, the cell cycle profile and invasive capability. Compared with control cells, the UBE2C transfected cells demonstrated increased cellular proliferation (p<0.05). UBE2C transfected cells also had a lower percentage in G1 phase and a higher percentage in S phase (p<0.05). Importantly, the UBE2C transfected cells had a notable enhancement of cell numbers penetrating the basement membrane compared with the control group (p<0.05). Ectopic up-regulation UBE2C promoted the growth of lung cancer cells in vivo. Furthermore, we found UBE2C increased the expression of cyclin D1 and MMP-2. These results show UBE2C may represent a potential therapeutic target for lung cancer.

• YAKHAK HOEJI
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• v.55 no.3
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• pp.267-272
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• 2011

Human NK cells, identified 30 years ago based on their ability to spontaneously kill tumor cells, constitute a subset of lymphocytes, which play an important role in the first line of immune defense and the effective function of these cells are enhanced by cytokines. Lung carcinoma has been one of the most commonly diagonosed cancer as well as the leading cause of cancer death in male. Here we provide the evidence that human natural killer cells has inhibitory effects on tumor growth of human lung cancer cell NCI-H460 (non-small cell lung cancer). Enriched NK cell population was obtained by 2 weeks cultivation in interleukin-2(IL-2)-containing medium. The resulting population comprised 26% CD3$^+$ cells, 9% CD3$^+$CD4$^+$ cells, 16% CD3$^+$CD8$^+$ cells, 76% CD56$^+$ cells, 6% CD3$^+$CD56$^+$ cells and 70% CD3$^-$CD56$^+$ cells. Activated NK cells at doese of 2.5, 5, and 10 million cells per mouse inhibited 2%, 12% and 45% of NCI-H460-induced tumor growth in nude mouse xenograft assays, repectively. This result suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for lung cancer patients.

• Molecules and Cells
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• v.37 no.9
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• pp.664-671
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• 2014

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.

• Journal of agriculture & life science
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• v.45 no.5
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• pp.91-96
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• 2011

We investigated the inhibitory effects of solvent extracts from Ailanthus altissima in A549 human lung cancer cell. A. altissima has been recognized as a traditional healthy food due to its various biological activities against hypertension, strokes, fever, pain, neuralgia, inflammation, and cancer effects. Recently, it has been reported that the extracts of various wild vegetables show strong anti-cancer properties by induction of apoptosis. However, the mechanisms of their cytotoxicity in human lung cancer cells have been poorly understood. The present study was investigated the effects of solvent extracts from A. altissima on cell growth and apoptosis on A549 human lung cancer cells. A treatment of A. altissima inhibited the growth of A549 cells in a dose-dependent manner by inducing apoptosis. Especially, the chloroform fraction showed the highest anti-cancer effect among five kinds of fractions. And also, induction of apoptosis by chloroform fraction were associated with down-regulation of Bcl-2, and up-regulation of pro-apoptotic Bax expression. From these results, A. altissima may have a therapeutic potential in human lung cancer cells and as a functional food.

• Biomolecules & Therapeutics
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• v.20 no.6
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• pp.513-519
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• 2012

Although the immense efforts have been made for cancer prevention, early diagnosis, and treatment, cancer morbidity and mortality has not been decreased during last forty years. Especially, lung cancer is top-ranked in cancer-associated human death. Therefore, effective strategy is strongly required for the management of lung cancer. In the present study, we found that novel daphnane diterpenoids, yuanhualine (YL), yuanhuahine (YH) and yuanhuagine (YG) isolated from the flower of Daphne genkwa (Thymelaeaceae), exhibited potent anti-proliferative activities against human lung A549 cells with the $IC_{50}$ values of 7.0, 15.2 and 24.7 nM, respectively. Flow cytometric analysis revealed that the daphnane diterpenoids induced cell-cycle arrest in the G0/G1 as well as G2/M phase in A549 cells. The cell-cycle arrests were well correlated with the expression of checkpoint proteins including the up-regulation of cyclin-dependent kinase inhibitor p21 and p53 and down-regulation of cyclin A, cyclin B1, cyclin E, cyclin dependent kinase 4, cdc2, phosphorylation of Rb and cMyc expression. In the analysis of signal transduction molecules, the daphnane diterpenoids suppressed the activation of Akt, STAT3 and Src in human lung cancer cells. The daphnane diterpenoids also exerted the potent anti-proliferative activity against anticancer-drug resistant cancer cells including gemcitabine-resistant A549, gefitinib-, erlotinib-resistant H292 cells. Synergistic effects in the growth inhibition were also observed when yuanhualine was combined with gemcitabine, gefitinib or erlotinib in A549 cells. Taken together, these findings suggest that the novel daphnane diterpenoids might provide lead candidates for the development of therapeutic agents for human lung cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8631-8635
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• 2014

Glutathione S-transferase A1 (GSTA1) appears to be primarily involved in detoxification processes, but possible roles in lung cancer remain unclear. The objective of this study was to investigate the expression and function of GSTA1 in lung cancer cells. Real-time PCR and Western blotting were performed to assess expression in cancer cell lines and the normal lung cells, then verify the A549 cells line with stable overexpression. Localization of GSTA1 proteins was assessed by cytoimmunofluorescence. Three double-strand DNA oligoRNAs (SiRNAs) were synthesized prior to being transfected into A549 cells with Lipofectamine 2000, and then the most efficient SiRNA was selected. Expression of the GSTA1 gene in the transfected cells was determined by real-time PCR and Western blotting. The viability of the transfected cells were assessed by MTT. Results showed that the mRNA and protein expression of A549 cancer cells was higher than in MRC-5 normal cells. Cytoimmunofluorescence demonstrated GSTA1 localization in the cell cytoplasm and/or membranes. Transfection into A549 cells demonstrated that down-regulated expression could inhibit cell viability. Our data indicated that GSTA1 expression may be a target molecule in early diagnosis and treatment of lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4755-4759
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• 2016

Introduction: Lung cancer is one of the most common cancers worldwide. In certain countries such as United States of America, it is the leading cause of related cancer mortality among both men and women. Natural products play an important role in overcoming the limitations of chemotherapy and radiotherapy. Objectives: In this study, we investigated the antiproliferative and apoptotic activities of Kanahia laniflora methanolic extract against human non-small cell lung cancer cells (A549). Methods: Sulforhodamine B colorimetric assays were used to determine the inhibitory effects of a leaf methanolic extract against A549 cells. Results: The extract showed strong cytotoxic activity against A549 cells with an $IC_{50}$ value of $0.13{\mu}g/ml$ compared to $0.21{\mu}g/ml$ for doxorubicin. The extract also significantly increased the percentage of apoptotic cells to 49.7% as compared to 1.4% and 47.4% for control and doxorubicin respectively. Conclusion: These results showed, for the first time, that a methanolic extract of Kanahia laniflora leaves can inhibit the proliferation of human non-small cell lung cancer cells (A549). Further attention to its potential as a new effective anticancer agent is warranted.