Endotoxin induces proliferation of NSCLC in vitro and in vivo: role of COX-2 and EGFR activation

Hattar, Katja; Savai, Rajkumar; Subtil, Florentine S. B.; Wilhelm, Jochen; Schmall, Anja; Lang, Dagmar S.; Goldmann, Torsten; Eul, Bastian; Dahlem, Gabriele; Fink, Ludger; Schermuly, Ralph Theo; Banat, Gamal Andre; Sibelius, Ulf; Grimminger, Friedrich; Vollmer, Ekkehard; Seeger, Werner; Grandel, Ulrich

doi:10.1007/s00262-012-1341-2

Cited by 47 publications

(47 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings suggest that LPS from E. coli 0111:B4 can promote A549 cell proliferation and induce oxidative stress and inflammation, which is consistent with previous studies (6,(31)(32)(33). Our data suggest that endotoxin is an applicable and powerful promoter of tumor cell proliferation.…”

Section: Discussionsupporting

confidence: 92%

“…Our data suggest that endotoxin is an applicable and powerful promoter of tumor cell proliferation. The escalation in metabolic activity was previously noted after 24 h of LPS treatment and A549 cells are well known to correspond to cellular proliferation (32). The obtained results indicate that beraprost treatment significantly reverse LPS-induced cell proliferation.…”

Section: Discussionsupporting

confidence: 72%

See 1 more Smart Citation

Beraprost sodium, a prostacyclin (PGI) analogue, ameliorateslipopolysaccharide-induced cellular injury in lung alveolar epithelial cells

Vicil¹,

Erdoğan²

2015

Turk J Med Sci

View full text Add to dashboard Cite

Background/aim: Human alveolar epithelial cells play a critical role in the pathogenesis of lung diseases. The objective of this study is to determine the contribution of beraprost sodium, a prostaglandin I 2 (PGI 2 ) analogue, to inflammatory and oxidative events in response to lipopolysaccharide (LPS) in airway epithelial cells.Materials and methods: Human pulmonary alveolar epithelial cells (A549) were pretreated with 10 µM beraprost sodium 30 min before stimulation with 1 µg/mL LPS for 24 h. The cellular viability assessments were evaluated by quantitative MTT test. Catalase activity and glutathione and lipid peroxidation levels were determined using spectrophotometric techniques. mRNA expression analyses were performed by real-time qRT-PCR. Results:The endotoxin induced a dose-dependent increase in proliferation of the cells, which was suppressed by the beraprost sodium treatment. LPS increased the expressions of TNF-α and IL-1β genes by 8-and 2.5-fold, respectively. It also induced lipid peroxidation and depleted cellular antioxidant capacity. Pretreatments of the cells with beraprost sodium significantly reversed the inflammation and suppressed oxidative stress. Conclusion:These findings suggest that beraprost sodium will provide a pivotal molecular basis for the design of new therapeutic strategies to cure endotoxin-induced lung injury, although additional comprehensive studies are still required.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 72%

Beraprost sodium, a prostacyclin (PGI) analogue, ameliorateslipopolysaccharide-induced cellular injury in lung alveolar epithelial cells

Vicil¹,

Erdoğan²

2015

Turk J Med Sci

View full text Add to dashboard Cite

show abstract

“…Celecoxib (CXB) is a cyclooxygenase 2-selective nonsteroidal anti-inflammatory drug (NSAID) that has been approved for the treatment of adult arthritis, and has been found to exhibit therapeutic effects on various types of cancers (19). Currently, CXB is widely being tested in clinical trials for its therapeutic activity against various cancers as a single agent and also in combination with other agents (20,21).…”

Section: Introductionmentioning

confidence: 99%

Combined cetuximab and celecoxib treatment exhibits a synergistic anticancer effect on human oral squamous cell carcinoma in vitro and in vivo

Qian¹,

Qian²,

Jing³

et al. 2014

Oncology Reports

View full text Add to dashboard Cite

Abstract. The aim of the present study was to evaluate the potency of epidermal growth factor receptor (EGFR) pathway inhibition achieved by combining cetuximab (CET), an anti-EGFR monoclonal antibody, and celecoxib (CXB), a cyclooxygenase-2 (COX-2) inhibitor, in oral squamous cell carcinoma (OSCC) in vitro and in vivo. The OSCC cell line, HSC3, was treated with CET (0-400 µg/ml), CXB (0-40 µM), or a combination of both at a range of concentrations. Cell proliferation, apoptosis, migration and invasion were determined to assess the anticancer effects in vitro. The in vivo effects of CET and CXB on tumor cell growth were examined using an OSCC xenograft nude mouse model. In addition, downstream protein expression levels of EGFR, p-EGFR, PI3K, p-PI3K, AKT and p-Akt were evaluated by western blot analysis. It was found that the combination of low concentrations of CET and CXB significantly suppressed the proliferation, migration and invasion of the HSC3 tumor cells and decreased PEG2 production and VEGF expression in vitro, and inhibited tumor growth in vivo compared to the action of either agent alone. The results also showed that this combination significantly induced apoptosis and increased caspase-3 and caspase-8 activity compared to the action of either agent alone (P<0.01). Furthermore, the combination treatment significantly reduced the expression of p-EGFR, p-PI3K and p-Akt in the HSC3 cell line, which may contribute to the inhibition of tumor growth. Taken together, our findings revealed that the additive combination of CET and CXB is a potential drug candidate for the treatment of OSCC. IntroductionOral squamous cell carcinoma (OSCC) accounts for approximately 4% of all carcinomas in men and 2% in women worldwide, with geographical variation in frequency (1). Although advances in early diagnosis and multimodal treatments, including surgery, chemotherapy and irradiation have been achieved, the 5-year survival rate of OSCC patients has remained at 50-60% due to recurrence and metastasis (2). Since conventional cytotoxic therapies act upon rapidly dividing normal cells as well as malignant cells, which results in the significant morbidity in patients with solid tumors including OSCC, this method is of limited benefit for survival (3). Therefore, the development of improved anticancer therapies that effectively and specifically target epithelial tumor cells while minimizing the toxic side effects commonly associated with conventional cytotoxic therapies is urgently needed.With the enhanced understanding of key cellular pathways involved in tumor growth, progression and cell death, molecular targeted therapies have been exploited (4). Recently, novel treatments aimed to target specific molecules, such as epidermal growth factor receptor (EGFR), aberrantly expressed in OSCC, have been investigated and tested in clinical trials at several research centers with promising results (5). For many years, the EGFR has been investigated as a major target for the treatment of uncontrolled tumor growth (6). The EGFR, a gl...

show abstract

“…The tumor volume was significantly greater than that of the A549 cells without LPS treatment and expression of the marker of proliferation, Ki-67, in tumor tissues was also significantly increased (18). Similarly, the in vivo data of the present study revealed that following grafting the MGC-803 gastric cancer cell line stimulated by LPS into the axilla of nude mice to establish tumor xenografts, there was an increase in tumor volume and weight in the LPS group, which was consistent with findings of a previous study (17).…”

Section: Discussionmentioning

confidence: 86%

CD14 knockdown reduces lipopolysaccharide-induced cell viability and expression of inflammation-associated genes in gastric cancer cells in vitro and in nude mouse xenografts

Zhang

Nie

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. The present study examined the role of CD14 in the regulation of lipopolysaccharide (LPS)-induced effects on gastric cancer cells. MGC-803 cells were stably transfected with CD14 short hairpin (sh)RNA and treated with LPS, followed by assessment of cell proliferation, apoptosis and gene expression using a cell counting kit-8 assay, flow cytometry, reverse transcription-polymerase chain reaction and western blot analysis, respectively. The cells subjected to CD14 knockdown were treated with 10 g/ml LPS and injected into nude mice to form tumor xenografts. CD14 shRNA-transfected MGC-803 cells did not exhibit any significant changes in cell viability compared with the control cells (P>0.05), but cell viability was markedly increased in the wild-type (WT) + LPS group (P<0.05). In contrast to the WT + LPS group, the cell viability of the sh-CD14 + LPS group was markedly decreased (P<0.05). In addition, compared with those in the controls, the level of sh-CD14 cell apoptosis did not change significantly; however, it was markedly reduced in the LPS group. Compared with that in the WT + LPS group, the rate of apoptosis in the sh-CD14 + LPS group increased to a certain extent, while it remained lower in the control group. In addition, compared with that in the control, the expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6 and IL-12, and human β-defensin 2 was significantly increased in the WT + LPS group, while, compared with that in the WT + LPS group, the expression of these genes was markedly reduced in the sh-CD14 + LPS group (P<0.05). The nude mouse experiments further confirmed the in vitro data, including the finding that LPS promoted the growth of xenografts, but knockdown of CD14 expression reduced the response of tumor cells to LPS treatment. In conclusion, LPS induced cell viability and the release of inflammatory cytokines, but inhibited gastric cancer cell apoptosis. Knockdown of CD14 expression had no significant effect on gastric cancer malignancy, but mediated LPS signal transduction. IntroductionGastric cancer is one of the most common types of cancer globally and accounted for 989,600 ovel cases and 738,000 cancer-associated fatalities in 2008 (1). >70% of novel gastric cancer cases and fatalities occur in the developing countries, while they have declined in the majority of developed countries, including countries in North America and Europe in previous decades (1). The risk factors for gastric cancer include Helicobacter (H.) pylori infection, history of tobacco smoking, and consumption of smoked foods, salted meat or fish and pickled vegetables. However, intake of fresh fruits and vegetables appears to lower the risk of gastric cancer (1). Regional variations in gastric cancer prevalence reflect the differences in dietary patterns and the prevalence of H. pylori infection (2). H. pylori is an aerobic Gram-negative bacterium found in the stomach, which causes chronic gastritis, peptic ulcers and gastric cancer. Thus, H. pylori infection has been classified as a class I carcinog...

show abstract

Endotoxin induces proliferation of NSCLC in vitro and in vivo: role of COX-2 and EGFR activation

Cited by 47 publications

References 50 publications

Beraprost sodium, a prostacyclin (PGI) analogue, ameliorateslipopolysaccharide-induced cellular injury in lung alveolar epithelial cells

Beraprost sodium, a prostacyclin (PGI) analogue, ameliorateslipopolysaccharide-induced cellular injury in lung alveolar epithelial cells

Combined cetuximab and celecoxib treatment exhibits a synergistic anticancer effect on human oral squamous cell carcinoma in vitro and in vivo

CD14 knockdown reduces lipopolysaccharide-induced cell viability and expression of inflammation-associated genes in gastric cancer cells in vitro and in nude mouse xenografts

Contact Info

Product

Resources

About