Targeting the KRAS, p38α, and NF-κB in lung adenocarcinoma cancer cells: The effect of combining RNA interferences with a chemical inhibitor.

Lung cancer is the leading cause of cancer-related death with less than 5-year survival rate for both men and women worldwide. KRAS (Kirsten rat sarcoma), nuclear factor-κB (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways have a critical role in the proliferation and progression of various cancers, including lung cancer. The p38 MAPK plays a different role in various tissue hence show a tissue-dependent behavior. It acts as an oncogene in some tissues while plays as a tumor suppressor in some other tissues. Also, KRAS and NF-κB act as an oncogene in various cancer. This study was dedicated to analyzing the combined effect of NF-κB inhibitor, specific KRAS, and p38α small interfering RNA (siRNA) in A549 cell line. The cytotoxic effects of p38α siRNA, KRAS siRNA, and NF-κB inhibitor were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay. Relative p38α, KRAS, and NF-κB messenger RNA (mRNA) levels were measured by quantitative reverse-transcription polymerase chain reaction. Induction of apoptosis by treatments was measured by fluorescence-activated cell sorting (FACS) analysis. The expression of mRNA related to p38α and KRAS genes was reduced to 23.4% and 26.7%, respectively, after treatment with specific siRNAs. Also, MTT assay showed that the cell viability after treatment with p38α siRNA, KRAS siRNA, NF-κB inhibitor and their combination was reduced. FACS results indicated that p38α siRNA, KRAS siRNA, and NF-κB inhibitor, and their combination, reduced the population of live cells in comparison with the population of untreated control cells (99.5%). The results are expressed as mean ± SD (n = 3); *P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001 vs control group. The results of this study indicated that p38α, KRAS, and NF-κB signaling pathways might play an important role in the development and growth of lung cancer and might be a potential therapeutic target for treatment of lung cancer.