Insulin action on H292 bronchial carcinoma cells as compared to normal bronchial epithelial cells

Mayer, Péter; Warnken, Mareille; Enzmann, Harald; Racké, Kurt

doi:10.1016/j.pupt.2011.12.005

Cited by 6 publications

(9 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Conduction of DNA chip hybridization was performed as described previously (Mayer et al 2012). In brief, samples were amplified and labeled using Low RNA Input Linear Amp Kit (Agilent Technologies, Santa Clara, CA, USA).…”

Section: Gene Expression Profilingmentioning

confidence: 99%

See 1 more Smart Citation

Non-small cell lung cancer cell survival crucially depends on functional insulin receptors

Frisch

Zimmermann

Zilleßen

et al. 2015

Endocrine-Related Cancer

Self Cite

View full text Add to dashboard Cite

Insulin plays an important role as a growth factor and its contribution to tumor proliferation is intensely discussed. It acts via the cognate insulin receptor (IR) but can also activate the IGF1 receptor (IGF1R). Apart from increasing proliferation, insulin might have additional effects in lung cancer. Therefore, we investigated insulin action and effects of IR knockdown (KD) in three (NCI-H292, NCI-H226 and NCI-H460) independent non-small cell lung cancer (NSCLC) cell lines. All lung cancer lines studied were found to express IR, albeit with marked differences in the ratio of the two variants IR-A and IR-B. Insulin activated the classical signaling pathway with IR autophosphorylation and Akt phosphorylation. Moreover, activation of MAPK was observed in H292 cells, accompanied by enhanced proliferation. Lentiviral shRNA IR KD caused strong decrease in survival of all three lines, indicating that the effects of insulin in lung cancer go beyond enhancing proliferation. Unspecific effects were ruled out by employing further shRNAs and different insulin-responsive cells (human pre-adipocytes) for comparison. Caspase assays demonstrated that IR KD strongly induced apoptosis in these lung cancer cells, providing the physiological basis of the rapid cell loss. In search for the underlying mechanism, we analyzed alterations in the gene expression profile in response to IR KD. A strong induction of certain cytokines (e.g. IL20 and tumour necrosis factor) became obvious and it turned out that these cytokines trigger apoptosis in the NSCLC cells tested. This indicates a novel role of IR in tumor cell survival via suppression of pro-apoptotic cytokines.

show abstract

Section: Gene Expression Profilingmentioning

confidence: 99%

“…In order to cover insulin actions caused by concentrations which are presumably achieved in the respiratory system after inhaling insulin (Mayer et al 2012), cells were treated with insulin in a range between 1 nM and 1 mM ( Fig. 2A).…”

Section: Effects Of Insulin On Cell Proliferation and Mitogenic Signamentioning

confidence: 99%

Non-small cell lung cancer cell survival crucially depends on functional insulin receptors

Frisch

Zimmermann

Zilleßen

et al. 2015

Endocrine-Related Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…This binding could potentially induce new-onset pulmonary cancer or accelerate growth of pre-existing malignant cells. Indeed, isolated human bronchial carcinoma cells (H292) were shown to express insulin receptors 4-5 times higher than normal bronchial epithelial cells[18]. In fact, the FDA requested the manufacturer to conduct a clinical trial with sufficient power to examine this issue.…”

Section: Safety Profile Of Timentioning

confidence: 99%

Place of technosphere inhaled insulin in treatment of diabetes

Mikhail¹

2016

WJD

View full text Add to dashboard Cite

Technosphere insulin (TI), Afrezza, is a powder form of short-acting regular insulin taken by oral inhalation with meals. Action of TI peaks after approximately 40-60 min and lasts for 2-3 h. TI is slightly less effective than subcutaneous insulin aspart, with mean hemoglobin A1c (HbA1c) reduction of 0.21% and 0.4%, respectively. When compared with technosphere inhaled placebo, the decrease in HbA1c levels was 0.8% and 0.4% with TI and placebo, respectively. Compared with insulin aspart, TI is associated with lower risk of late post-prandial hypoglycemia and weight gain. Apart from hypoglycemia, cough is the most common adverse effect of TI reported by 24%-33% of patients vs 2% with insulin aspart. TI is contraindicated in patients with asthma and chronic obstructive pulmonary disease. While TI is an attractive option of prandial insulin, its use is limited by frequent occurrence of cough, need for periodic monitoring of pulmonary function, and lack of long-term safety data. Candidates for use of TI are patients having frequent hypoglycemia while using short-acting subcutaneous insulin, particularly late post-prandial hypoglycemia, patients with needle phobia, and those who cannot tolerate subcutaneous insulin due to skin reactions.

show abstract

“…Lung cancer rates with Exubera summarized in the FDA briefing documents are of concern, as exposed patients had more than 5‐fold more lung cancer than comparators, albeit with small numbers of cases. An in vitro study of insulin action on H292 bronchial carcinoma cells showed that, as with many cancers, there was a 4–5‐fold increase in insulin receptor expression, and a 6‐fold increase in sensitivity to insulin's mitogenic effect over that of normal bronchial epithelium . One presumes there will be greater pulmonary exposure to insulin administered by inhalation than by systemic injection, so that a growth‐promoting effect on existing preclinical lesions could be a concern.…”

mentioning

confidence: 99%

“…是否有患肺癌的风险？有2名使用Afrezza治疗的患者，其中1名在临床对照试验期间，另外1名在随后的扩展试验期间发生了肺癌，每1000名患者每年的发生率为0.8例，与美国人群中的发生率相似。在FDA简报文件中总结的与Exubera有关的肺癌发生率使人担心，与对照组相比使用Exubera治疗的患者肺癌发生率高5倍，虽然只有很少的病例出现肺癌。在一项调查胰岛素对H292支气管癌细胞影响的体外研究中发现，与许多其他的癌症相似，与正常的支气管上皮细胞相比，支气管癌细胞的胰岛素受体表达增加了4–5倍，胰岛素促有丝分裂作用的敏感性增加了6倍。有一种假设就是与通过全身注射给药相比较，通过吸入给药后肺部的胰岛素浓度将更高，因此可能使人担心它对现有的临床前期病变具有促生长作用。然而，按照顾问委员会的效能计算公式，一项随机临床试验若要检测出使用吸入型胰岛素治疗后肺癌风险增加2倍，估计需要超过60000名的参与者治疗多年以后才能达到这个目标——这远远超过了赞助商的合理预期。…”

unclassified

Afrezza: Some questions about a new approach to prandial insulin 关于一种新型餐时胰岛素的一些问题

Bloomgarden

2014

Journal of Diabetes

View full text Add to dashboard Cite

Insulin action on H292 bronchial carcinoma cells as compared to normal bronchial epithelial cells

Cited by 6 publications

References 47 publications

Non-small cell lung cancer cell survival crucially depends on functional insulin receptors

Non-small cell lung cancer cell survival crucially depends on functional insulin receptors

Place of technosphere inhaled insulin in treatment of diabetes

Afrezza: Some questions about a new approach to prandial insulin 关于一种新型餐时胰岛素的一些问题

Contact Info

Product

Resources

About