Finally, the potential role of the natural agents and synthetic derivatives of natural compounds with anti-cancer activity, e.g. curcumin, CDF, and BR-DIM is highlighted in overcoming therapeutic resistance, suggesting that the above mentioned agents could be important for better treatment of lung cancer in combination therapy.
Incubation of colon and lung cancer cell lines with IL6, but not other cytokines, caused hMSH3, but no other mismatch repair proteins, to move from the nucleus to the cytosol after generation of oxidative stress; inhibition of IL6 signaling prevented this shift.
On logistic regression analysis, IL6 (interleukin 6), IL7R, IL15, TNF (tumor necrosis factor), and IL10 SNP were associated with risk of non-small cell lung cancer among African-Americans; IL7R and IL10 SNPs were also associated with risk of lung cancer among Caucasians.
Interestingly, IL-6 levels were significantly higher in sera of antibody-positive lung cancer patients compared with antibody-negative patients and controls.
Lung cancer patients exhibited significantly elevated serum IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 levels compared to controls (P<0.05) and most of these adipocytokines revealed a modest discriminative ability for the diagnosis of lung cancer, while BDNF were lower in patients (P<0.05).
Comparably, luciferase reporter assays of A549 lung cancer cell lines transfected with the CC haplotype revealed that the two-SNP haplotype had significantly higher IL-6 transcriptional activity compared with cells transfected with the common haplotype.
Our results suggest that JAK1 is responsible for STAT3 activation in lung cancer cells and that indirect attacks on JAK1-STAT3 using an IL-6 neutralizing antibody with or without EGFR inhibition can inhibit lung cancer growth in lung cancer subsets.
Mechanistic investigations revealed elevation in the lung of soluble IL6 receptor (sIL6R), the key driver of IL6 trans-signaling, and blocking this mechanism via interventions with an anti-IL6R antibody or the inhibitor sgp130Fc ameliorated lung cancer pathogenesis.
Single nucleotide polymorphisms (SNPs) in IL-6, IL6-R, and IL6-ST genes were assessed in 120 controls and 120 patients with confirmed lung cancer diagnosis.
Higher level of interleukin-6 (IL-6) existed in lung cancer patients and mutant EGFR and TGFβ signal requires the upregulation of IL-6 through the gp130/JAK pathway to overactive STAT3, an oncogenic protein which has been considered as a potential target for cancer therapy.
This in-depth study not only helped to elucidate the mechanism of how IL-6 promotes lung cancer but also provided new ideas and entry points to resolve the low specificity and sensitivity of lung cancer-related tumour markers.
Interleukin-6 (IL-6) can activate downstream signaling pathways in lung cancer cells, such as the STAT3 pathway, and is reported to be produced by tumor cells with activating EGFR mutations.
We found that the TNF-α and IL-6 polymorphisms may be a critical risk for the genetic susceptibility to lung cancers in the ethnic group Han of North China.