High dose human insulin and insulin glargine promote T24 bladder cancer cell proliferation via PI3K-independent activation of Akt

Liu, S.; Li, Y.; Lin, Tianxin; Fan, Xiaolong; Liang, Ye‐Lin; Heemann, Uwe

doi:10.1016/j.diabres.2010.11.009

Cited by 36 publications

(29 citation statements)

References 27 publications

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“…Ferguson et al (2012) have recently shown that high systemic insulin levels promote breast cancer metastasis in a hyperinsulinemic mouse model by activating c-myc signaling. It has been shown that high-dose human insulin and its analogs promoted T24 (bladder cancer cell), , and PC-3 (prostate cancer cell) proliferation (Weinstein et al 2009, Liu et al 2011b. These reports indicate that metabolic changes occurring in patients with hyperglycemia and hyperinsulinemia lead to increased susceptibility of breast cancer progression.…”

Section: Introductionmentioning

confidence: 83%

High glucose and insulin differentially modulates proliferation in MCF-7 and MDA-MB-231 cells

Gupta

Tikoo

2013

Journal of Molecular Endocrinology

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Various preclinical and clinical studies have linked diabetes and breast cancer, but little is known regarding the molecular mechanism involved. This study aimed to investigate the effect of high glucose and insulin in breast cancer cells (MCF-7: non-invasive, hormone dependent, and MDA-MB-231: invasive, hormone independent). In contrast to MCF-7 cells, high glucose augmented proliferation of MDA-MB-231 cells as observed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and bromodeoxyuridine assays. The high-glucose condition led to increased expression of cyclin D1, de-phosphorylation of p38, and increased phosphorylation of ERK in MDA-MB-231 cells but not in MCF-7 cells. Interestingly, we observed increased phosphorylation of GSK-3b, NF-kB, and ERa only in MCF-7 cells, highlighting their role as potential targets in prevention of progression of breast cancer under a high-glucose and insulin condition. Furthermore, insulin treatment under a high-glucose condition resulted in increased histone H3 phosphorylation and de-acetylation only in MDA-MB-231 cells. Taken together, we provide the first evidence that high glucose and insulin promotes proliferation of MDA-MB-231 cells by differential alteration of GSK-3b, NF-kB, and ERa expression and histone H3 modifications, which may directly or indirectly modulate the expression of genes involved in its proliferation.

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Section: Introductionmentioning

confidence: 83%

High glucose and insulin differentially modulates proliferation in MCF-7 and MDA-MB-231 cells

Gupta

Tikoo

2013

Journal of Molecular Endocrinology

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“…Previous studies have demonstrated that insulin may contribute to the proliferation and survival of different types of cancer, including gastric, colon, pancreatic, breast and bladder cancer (14,15,21,26). It has also been demonstrated that insulin potentiates the ability of lysophosphatidic acid to stimulate cell cycle progression and DNA synthesis in MCF-7 breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…The activated PI3K/Akt signaling pathway is involved in various oncogenic functions, including the induction of cell proliferation, migration and drug resistance (19). Previous studies have demonstrated that insulin promotes the proliferation of pancreatic, bladder, breast and colon cancer cells via the PI3K/Akt signaling pathway (13,14,21). In NSCLC, overexpression of InsR predicts poor patient survival (29).…”

Section: Discussionmentioning

confidence: 99%

“…To further explore the mechanism of insulin on cell proliferation, migration and drug sensitivity, the effect of insulin on the IRS and PI3K/Akt signaling pathway in NSCLC, which has been investigated in other types of cancer (14,21), was determined by western blot analysis. The results demonstrated that insulin increased p-Akt and p-IRS1 expression in a dose-dependent manner (Fig.…”

Section: Insulin Increases the Resistance Of Nsclc Cells To Ddpmentioning

confidence: 99%

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Oncogenic activity of insulin in the development of non‑small cell lung carcinoma

et al. 2017

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Abstract. Insulin is associated with the progression of numerous different types of cancer. However, the association between insulin and non-small cell lung carcinoma (NSCLC) remains unknown. The aim of the present study was to evaluate the role of insulin in the proliferation, migration and drug resistance of NSCLC cells, and to determine whether the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway was involved. NSCLC cells were treated with insulin in the absence or presence of LY294002, an inhibitor of the PI3K/Akt pathway. Following co-incubation with insulin, cell proliferation and drug resistance were measured by MTT; cell migration was examined by wound healing and Transwell assays; and the expression of cyclin A, proliferating cell nuclear antigen (PCNA), p27, matrix metalloproteinase 3 (MMP3), P-gp and proteins involved in the PI3K/Akt pathway were assessed via western blotting. The results of the current study demonstrated that insulin enhanced the proliferation, migration and drug resistance of NSCLC cells. Correspondingly, insulin upregulated the expression of cyclin A, PCNA, MMP3, P-gp and downregulated p27 expression in NSCLC cells. Following treatment with insulin, it was demonstrated that phospho-Akt expression increased in a dose-dependent manner. However, the effects of insulin on NSCLC cells was inhibited by the PI3K/Akt pathway inhibitor LY294002. Therefore, the results of the current study indicate that insulin is associated with the development of NSCLC by activating the PI3K/Akt pathway. This may improve understanding of the mechanism of action of insulin in NSCLC in the future.

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“…The biological mechanism underlying the relationship between DM and its potential promoting effect on urothelial cells is under investigation. In an in vitro experiment, urothelial proliferation was promoted by high-dose insulin [20]. Expression of IGF-receptor I, which can promote cell growth and antiapoptosis, has been reported in invasive urothelial carcinoma of the bladder [21].…”

Section: Discussionmentioning

confidence: 99%

Poor Preoperative Glycemic Control Is Associated with Dismal Prognosis after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Korean Multicenter Study

et al. 2016

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PurposeThe purpose of this study is to evaluate the effect of diabetes mellitus (DM) and preoperative glycemic control on prognosis in Korean patients with upper tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy (RNU).Materials and MethodsA total of 566 patients who underwent RNU at six institutions between 2004 and 2014 were reviewed retrospectively. Kaplan-Meier and Cox regression analyses were performed to assess the association between DM, preoperative glycemic control, and recurrence-free, cancer-specific, and overall survival.ResultsThe median follow-up period was 33.8 months (interquartile range, 41.4 months). A total of 135 patients (23.8%) had DM and 67 patients (11.8%) had poor preoperative glycemic control. Patients with poor preoperative glycemic control had significantly shorter median recurrence-free, cancer-specific, and overall survival than patients with good preoperative glycemic control and non-diabetics (all, p=0.001). In multivariable Cox regression analysis, DM with poor preoperative glycemic control showed association with worse recurrence-free survival (hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.31 to 3.90; p=0.003), cancer-specific survival (HR, 2.96; 95% CI, 1.80 to 4.87; p=0.001), and overall survival (HR, 2.13; 95% CI, 1.40 to 3.22; p=0.001).ConclusionDiabetic UTUC patients with poor preoperative glycemic control had significantly worse oncologic outcomes than diabetic UTUC patients with good preoperative glycemic control and non-diabetics. Further investigation is needed to elucidate the exact mechanism underlying the impact of glycemic control on UTUC treatment outcome.

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High dose human insulin and insulin glargine promote T24 bladder cancer cell proliferation via PI3K-independent activation of Akt

Cited by 36 publications

References 27 publications

High glucose and insulin differentially modulates proliferation in MCF-7 and MDA-MB-231 cells

High glucose and insulin differentially modulates proliferation in MCF-7 and MDA-MB-231 cells

Oncogenic activity of insulin in the development of non‑small cell lung carcinoma

Poor Preoperative Glycemic Control Is Associated with Dismal Prognosis after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Korean Multicenter Study

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