Lung cancer chemoprevention: difficulties, promise and potential agents?

Dragnev, K.; You, Ming; Wang, Yian; Lubet, Ronald A.

doi:10.1517/13543784.2013.731392

Cited by 17 publications

(11 citation statements)

References 72 publications

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“…In addition, epidemiologic data show that aspirin, celecoxib, and other NSAIDs exert chemopreventive effects on lung cancer as well as several other types of epithelial tumors (9)(10)(11). Recent studies found that NSAIDs may exert anticancer activities in both COX-dependent and -independent manners, including suppressing E2F1, Mcl-1, and survivin and activating the eIF2a kinase PKR in various cancer cells (12,47,48).…”

Section: Mir-101 Elicits Its Antitumor Activity Through Targeting Lin28bmentioning

confidence: 99%

“…Cyclooxygenase-2 (COX2), a member of the COXs that are responsible for the production of inflammatory mediator prostaglandins, has been identified as a key inflammation-associated molecule in response to cigarette smoking, cytokines, and growth factors, and COX2 is known to promote the initiation and progression of NSCLC as well as other types of human epithelial tumors (3)(4)(5)(6)(7). Interestingly, inhibition of COX2 by nonsteroid anti-inflammatory drugs (NSAID) has been shown to be an effective approach in prevention and therapy of NSCLC and several other types of cancers by both epidemiologic and experimental data (8)(9)(10)(11)(12)(13). Such findings have confirmed the role of inflammation in the pathogenesis of NSCLC, but the molecular connections between inflammation and NSCLC have remained largely elusive.…”

Section: Introductionmentioning

confidence: 99%

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IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis

et al. 2014

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Inflammatory stimuli clearly contribute to lung cancer development and progression, but the underlying pathogenic mechanisms are not fully understood. We found that the proinflammatory cytokine IL-1b is dramatically elevated in the serum of patients with non-small cell lung cancer (NSCLC). In vitro studies showed that IL-1b promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1b acted through the COX2-HIF1a pathway to repress the expression of microRNA-101 (miR-101), a microRNA with an established role in tumor suppression. Lin28B was identified as critical effector target of miR-101 with its repression of Lin28B, a critical aspect of tumor suppression. Overall, IL-1b upregulated Lin28B by downregulating miR-101. Interestingly, cyclooxygenase-2 inhibition by aspirin or celecoxib abrogated IL-1b-mediated repression of miR-101 and IL-1b-mediated activation of Lin28B along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined an IL-1b-miR-101-Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC. Cancer Res; 74(17); 4720-30. Ó2014 AACR.

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Section: Mir-101 Elicits Its Antitumor Activity Through Targeting Lin28bmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis

et al. 2014

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“…Histologically, lung cancer can be classified into small-cell lung cancer and non-small cell lung cancer (NSCLC) with 80–85% being NSCLC (Dragnev et al , 2013), most of which are diagnosed at an advanced stage of the disease and have a poor long-term survival from curative surgery or radiation therapy (Marquez-Medina and Popat, 2016). In particular, mutated and overactive epidermal growth factor receptor (EGFR) in NSCLC has emerged as a unique subset of lung adenocarcinoma (Koehler and Schuler, 2013), and targeting the dysregulated EGFR with tyrosine kinase inhibitors (TKIs) have been developed to treat locally advanced or metastatic NSCLC (Lee et al , 2013).…”

Section: Introductionmentioning

confidence: 99%

Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells

Liu

Gao

2017

Toxicology and Applied Pharmacology

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has demonstrated dramatic clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of acquired drug resistance. The aim of this study was to explore the potential utility of chromosome region maintenance 1 (CRM1) inhibitor leptomycin B (LMB) in combination with gefitinib to overcome primary and acquired gefitinib resistance in NSCLC cells. The combinative effects of gefitinib and LMB were evaluated by MTT and its underlining mechanism was assessed by flow cytometry and Western blot. LMB displayed a synergistic effect on gefitinib- induced cytotoxicity in A549 (IC50: 25.0±2.1 μM of gefitinib+LMB vs. 32.0±2.5 μM of gefitinib alone, p<0.05). Gefitinib+LMB caused a significantly different cell cycle distribution and signaling pathways involving in EGFR/survivin/p21 compared with gefitinib. A549 cells then were treated with progressively increasing concentrations of gefitinib (A549GR) or in combination with LMB (A549GLR) over 10 months to generate gefitinib resistance. IC50 of gefitinib in A549GLR (37.0±2.8 μM) was significantly lower than that in A549GR (53.0±3.0 μM, p<0.05), which indicates that LMB could reverse gefitinib-induced resistance in A549. Further mechanism investigation revealed that the expression patterns of EGFR pathway and epithelial- mesenchymal transition (EMT) markers in A549, A549GR, and A549GLR were significantly different. In conclusion, LMB at a very low concentration combined with gefitinib showed synergistic therapeutic effects and ameliorated the development of gefitinib- induced resistance in lung cancer cells.

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“…Despite significant advances in chemotherapeutic, radiotherapeutic, and targeted treatment approaches for lung cancer, the longterm survival of patients with advanced-stage lung cancer remains low (2). To date, human prevention trials in the area of lung cancer have shown minimal promise (3). Thus, there is a need for identifying new chemopreventive agents with novel mechanisms of action for prevention of lung cancer.…”

Section: Introductionmentioning

confidence: 99%

β-Escin Inhibits NNK-Induced Lung Adenocarcinoma and ALDH1A1 and RhoA/Rock Expression in A/J Mice and Growth of H460 Human Lung Cancer Cells

Patlolla

Biddick

et al. 2013

Cancer Prevention Research

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Lung cancer is the leading cause of cancer-related deaths. b-Escin, a triterpene saponin isolated from horse chestnut seeds, was tested for inhibition of lung adenoma and adenocarcinoma induced by the tobacco carcinogen 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice; and its possible mode of action was evaluated using the H460 human lung cancer cell line. At 6 weeks of age, 35 mice were fed AIN-76A-modified diet, and one week later, lung tumors were induced with a single intraperitoneal (i.p.) injection of 10 mmol NNK/mouse. Three weeks after the NNK treatment, groups of mice were fed either control or experimental diets containing 500 ppm for 20 weeks (10 control, 5 b-escin) or 36 weeks (15 control, 5 b-escin) and evaluated for lung tumor via histopathologic methods. Administration of 500 ppm b-escin significantly suppressed lung tumor (adenoma þ adenocarcinoma) formation by more than 40% (P < 0.0015) at 20 weeks and by 53.3% (P < 0.0001) at 37 weeks. b-Escin inhibited NNK-induced lung adenocarcinoma formation by 65% (P < 0.001) at 20 weeks and by 53% (P < 0.0001) at 37 weeks. Immunohistochemical analysis revealed that lung tumors from mice exposed to b-escin showed significantly reduced aldehyde dehydrogenase (ALDH)1A1 and phospho-Akt (p-Akt) expression when compared with those in mice fed control diet. Aldefluor assay for ALDH revealed that among H460 lung cancer cells treated with different concentrations of b-escin (0-40 mmol/L), the subpopulation of cells with elevated ALDH activity was inhibited significantly. Our findings suggest that b-escin inhibits tobacco carcinogeninduced lung tumor formation by modulating ALDH1A1-positive cells and RhoA/Rock signaling. Cancer Prev Res; 6(10);

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Lung cancer chemoprevention: difficulties, promise and potential agents?

Cited by 17 publications

References 72 publications

IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis

IL-1β-Mediated Repression of microRNA-101 Is Crucial for Inflammation-Promoted Lung Tumorigenesis

Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells

β-Escin Inhibits NNK-Induced Lung Adenocarcinoma and ALDH1A1 and RhoA/Rock Expression in A/J Mice and Growth of H460 Human Lung Cancer Cells

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