New basic approach to treat non‐small cell lung cancer based on RNA‐interference

Abstract

Background: To date the therapy for non-small cell lung cancer (NSCLC) is associated with severe side effects, frustrating outcomes, and does not consider different tumor characteristics. The RNA-interference (RNAi) pathway represents a potential new approach to treat NSCLC. With small interfering ribonucleic acids (siRNAs), it is possible to reduce the expression of proliferation-dependent proteins in tumor cells, leading to their apoptosis. We propose that siRNAs could be adapted to the tumor type and may cause fewer side effects than current therapy. Methods: Four NSCLC cell lines were cultured under standard conditions and transfected with three different concentrations of siRNAs targeted against the hypoxia-inducible factors 1α and 2α (HIF1α and HIF2α) and signal transducer and activator of transcription 3 (STAT3). The expression was observed by quantitative real-time polymerase chain reaction and western blots. For the analysis of cell growth three days after transfection, the cell number was detected using a CASY cell counter system. Results:The results of the silencing of the analyzed factors differ in each cell line. Cell growth was significantly reduced in all cell lines after transfection with HIF1α-and STAT3-siRNA. The silencing of HIF2α resulted in a significant effect on cell growth in squamous, and large-cell lung cancer. Conclusions: This study shows that the knockdown and viability to siRNA transfection differ in each tumor type according to the used siRNA. This implies that the tumor types differ among themselves and should be treated differently. Therefore, the authors suggest a possible approach to a more personalized treatment of NSCLC.

The emerging role of estrogen related receptorα in complications of non‑small cell lung cancers (Review)

“…These signals are accompanied by suppressed inhibitory signals mediated by tumor suppressor proteins including p21, p27, p53, pRB and PTEN. NSCLC cell culture-based investigations demonstrated ERRα specific inverse agonists/small interfering (si) RNA/shRNA effect cell cycle regulation (144). In one such investigation using NSCLC A549 cells, Wang et al (140) noticed significant alterations in mitochondrial mass, mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS) generation following the administration of the ERRα inverse agonist XCT-790.…”

Targeting Estrogens and Various Estrogen-Related Receptors against Non-Small Cell Lung Cancers: A Perspective

“…The in vitro cell culture based experiments documented an ERRα role in cell proliferation and migration. An investigation by Makowiecki and colleagues monitored the effects of ERRα-specific inverse agonists/small interfering (si) RNA/shRNA on cell-cycle regulation [ 191 ]. In a similar observation, Wang and associates reported that in the in vitro cultured A549 NSCLC cells, ERRα affects the mitochondrial physiology and quenches ROS generation which suppressed the tumor suppressor protein p53 and pRB expressions.…”

Signal transducers and activators of transcription 3 function in lung cancer

“…The recently discovered microRNAs control diverse aspects of cell function, including immune regulation. [74] The type-2-skewing TME induces the down-regulation of miR-17-92 expression in T cells, thereby diminishing the persistence of tumor-specific T cells and tumor control. Genetic engineering of T cells to express miR-17-92 may represent a promising approach for cancer immunotherapy.…”