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

Abstract

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.

Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

“…Is it possible that IR-A or IGF1R activation may have deleterious consequences because it triggers proliferation? On the one hand, there is some data about these receptors being involved in carcinogenesis, so strategies for treating some tumors based on inhibition of IGF1R and IR-A are being developed [ 299 , 301 , 302 , 303 ]. On the other hand, promising medications for treating various diseases were designed based on IGF-1 (another IGF1R ligand) and these substances are already under evaluation in clinical studies [ 304 , 305 , 306 ].…”

Human Insulin Therapy Is Associated With an Increased Risk of Lung Cancer: A Population-Based Retrospective Cohort Study

“…Some basic research provides possible explanations. An in vitro study using non-small-cell lung cancer cells suggested that insulin promotes the proliferation, migration, and invasion of lung cancer by increasing the phosphorylation of IR substrate 1 and activating the phosphoinositide 3-kinase/protein kinase B pathway (12). Another study showed that ablation of IR substrates 1 and 2 suppressed Kras -driven lung tumorigenesis (13).…”

Based on network pharmacology, using methods such as molecular docking and gene difference analysis, small molecule compounds for the treatment of lung adenocarcinoma and lung squamous cell carcinoma were screened in saussurea involucrata, and new therapeutic targets were discovered

“…Studies have shown that insulin can up-regulate the expression of MMP3 genes in NSCLC cells, but its expression will be affected by PI3K/Akt. Inhibited by pathway inhibitors (29).…”