Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells

Yi, Hee; Cho, Hee-Jung; Cho, Soo‐Min; Jo, Kyul; Park, Jina; Lee, Soo-Han; Chang, Byung-Joon; Kim, Jin-Suk; Shin, Ho‐Chul

doi:10.4196/kjpp.2012.16.1.11

Cited by 23 publications

(19 citation statements)

References 25 publications

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“…Several experimental studies have demonstrated that IL-6 promotes tumorigenesis, angiogenesis, metastasis, and treatment resistance [36]–[39]. Moreover, the early evidence suggests that IL-6 may have an important role in the CSC phenotype and function [40], similar to the other recent findings documenting that lung CSC-like cells have a high level of expression of IL-6/IL-6R [38]. Additionally, IL-6 has been shown to enhance tumorigenicity in glioblastoma, consistent with an increase in the CSC self-renewal capacity [41], [42].…”

Section: Discussionsupporting

confidence: 53%

Hypoxia-Induced Aggressiveness of Pancreatic Cancer Cells Is Due to Increased Expression of VEGF, IL-6 and miR-21, Which Can Be Attenuated by CDF Treatment

et al. 2012

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Hypoxia is known to play critical roles in cell survival, angiogenesis, tumor invasion, and metastasis. Hypoxia mediated over-expression of hypoxia-inducible factor (HIF) has been shown to be associated with therapeutic resistance, and contributes to poor prognosis of cancer patients. Emerging evidence suggest that hypoxia and HIF pathways contributes to the acquisition of epithelial-to-mesenchymal transition (EMT), maintenance of cancer stem cell (CSC) functions, and also maintains the vicious cycle of inflammation-all which lead to therapeutic resistance. However, the precise molecular mechanism(s) by which hypoxia/HIF drives these events are not fully understood. Here, we show, for the first time, that hypoxia leads to increased expression of VEGF, IL-6, and CSC signature genes Nanog, Oct4 and EZH2 consistent with increased cell migration/invasion and angiogenesis, and the formation of pancreatospheres, concomitant with increased expression of miR-21 and miR-210 in human pancreatic cancer (PC) cells. The treatment of PC cells with CDF, a novel synthetic compound inhibited the production of VEGF and IL-6, and down-regulated the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 and miR-210 under hypoxia. CDF also led to decreased cell migration/invasion, angiogenesis, and formation of pancreatospheres under hypoxia. Moreover, CDF decreased gene expression of miR-21, miR-210, IL-6, HIF-1α, VEGF, and CSC signatures in vivo in a mouse orthotopic model of human PC. Collectively, these results suggest that the anti-tumor activity of CDF is in part mediated through deregulation of tumor hypoxic pathways, and thus CDF could become a novel, and effective anti-tumor agent for PC therapy.

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Section: Discussionsupporting

confidence: 53%

Hypoxia-Induced Aggressiveness of Pancreatic Cancer Cells Is Due to Increased Expression of VEGF, IL-6 and miR-21, Which Can Be Attenuated by CDF Treatment

et al. 2012

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“…Some evidence suggested that anti-metabolite cancer drugs can lead to propagation of CSCs (Yi et al, 2012). Accordingly, chemotherapy drug-induced tumor cells might be an effective way to obtain CSC-like cells.…”

Section: Discussionmentioning

confidence: 99%

Gene and protein expression in the oxaliplatin-resistant HT29/L-OHP human colon cancer cell line

2015

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ABSTRACT. Oxaliplatin (L-OHP) is one of the most commonly used anticancer drugs in adjuvant treatment of colon cancer after complete resection of the primary tumor and treatment of metastatic colorectal cancer. Cancer cells eventually become resistant to L-OHP, which diminishes its curative effect. However, the mechanism of action of L-OHP remains unknown. In this study, an L-OHP-resistant human colon cancer cell line, HT29/L-OHP, was established by gradually increasing the dose of L-OHP in culture. The expression levels of the tumor susceptibility gene 101 (tsg101) and the TSG101 protein in HT29 and HT29/L-OHP cell lines were examined by reverse transcriptionpolymerase chain reaction and western blot analysis. In addition, the expression levels of several apoptosis-regulating protein markers were determined using immunohistochemistry-staining assays. We found that the expression of tsg101 mRNA and of TSG101 protein were (2015) significantly higher in the HT29/L-OHP cell line than in its parent, HT29 (P < 0.05). In addition, the expression of multiple apoptosisregulating protein markers were significantly increased (P < 0.05) in the HT29/L-OHP cell line. These data suggest that these markers could be useful as predictive markers for evaluating and comparing the efficacy and molecular pharmacology of chemotherapeutics.

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“…Cisplatin‐selected cells were more resistant to the selecting agent and also possessed multidrug resistance to other chemotherapeutic agents . In various studies in tumour cell lines, incubation with cisplatin led to enrichment of cell populations expressing CSLC markers . The enriched populations also presented increased clonogenic ability, capacity to form tumour spheres, migratory ability, increased tumourigenicity and metastatic potential .…”

Section: Therapy‐enrichment Of Lung Cancer Stem‐like Cellsmentioning

confidence: 99%

Therapy‐induced enrichment of putative lung cancer stem‐like cells

Freitas

Teixeira

Santos-Silva

et al. 2013

Intl Journal of Cancer

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Tumour drug resistance is a major issue in the management of lung cancer patients as almost all lung tumours are either intrinsically resistant or quickly develop acquired resistance to chemotherapeutic drugs. Cancer drug resistance has recently been linked, at least in part, to the existence of cancer stem-like cells (CSLCs), a small sub-population of cells within the tumour that possess stem-like properties. CSLCs are often isolated by fluorescence activated cell sorting (FACS) according to the expression of certain stem-like cell membrane markers. Conflicting results regarding the specificity of particular stem cell surface markers for isolating CSLCs have, however, been recently reported. Therefore, alternative strategies enabling the identification and study of CSLCs should be considered, particularly in tumour types where appropriate stem cell markers are not well established and validated, like in lung cancer. In this article, we review data indicating therapy-selection as a valid approach for putative lung CSLCs enrichment. We believe that this strategy would be determinant for correctly assessing and characterising the sub-populations of CSLCs that are able to survive chemo or radiotherapy regimens and, at the same time, also have the ability to recapitulate and sustain tumour growth. Using therapy-induced enrichment of CSLCs may, therefore, prove to be an extremely useful method for studying CSLCs and provide new clues regarding potential therapeutic targets for their efficient elimination, which will undoubtedly play a decisive role in improving lung cancer patients' survival. Lung Cancer and Therapy ResistanceOver the last decades, our understanding of human cancer development has greatly increased and much progress has been made regarding cancer therapy. Nevertheless, our ability to develop clinically effective therapies based on this knowledge has had limited success. 1 After an apparently successful initial therapy, many tumours often relapse in a more aggressive form than the original tumour. Lung cancer is the worldwide leading cause of cancer-related deaths and one of the most incurable cancers due to late presentation, disease relapse and low rate of curative therapy. 2 Indeed, after an apparent good response to initial therapy, lung cancer has a particularly poor prognosis with 5-year survival lower than 15%. 3 There are two main types of lung cancer, small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). About 15% of lung tumours are SCLCs and arise in the

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Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells

Cited by 23 publications

References 25 publications

Hypoxia-Induced Aggressiveness of Pancreatic Cancer Cells Is Due to Increased Expression of VEGF, IL-6 and miR-21, Which Can Be Attenuated by CDF Treatment

Hypoxia-Induced Aggressiveness of Pancreatic Cancer Cells Is Due to Increased Expression of VEGF, IL-6 and miR-21, Which Can Be Attenuated by CDF Treatment

Gene and protein expression in the oxaliplatin-resistant HT29/L-OHP human colon cancer cell line

Therapy‐induced enrichment of putative lung cancer stem‐like cells

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