Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway.

Abstract

Lung cancer is considered the most ubiquitous malignant form of cancer, and the current treatment strategies do not offer effective outcomes to the patients. The present study examined the effectiveness of natural drugs delphinidin (DN) and oroxylin A (OA) in inhibiting the development of lung cancer cells (A549) through the blocking of the Signal transducer and activator of transcription 3 (STAT3) and focal adhesion kinase (FAK) intervene signaling pathways. These included cytotoxicity assessments, reactive oxygen species (ROS) levels, apoptotic morphological features, mitochondrial membrane potential (ΔΨm), nuclear fragmentation, and cell cycle analysis. Furthermore, the combination of DN and OA treatments on the expression of STAT-3, FAK, and various proliferation and apoptotic proteins was studied using western blotting. The results we have obtained are that the combination of DN and OA causes significant cytotoxicity, ROS, alteration of ΔΨm, and nuclear fragmentation, resulting in apoptosis of A549 cells. Furthermore, A549 cells treated with DN and OA concurrently displayed increased cell cycle arrest at the G2/M phase. Additionally, the combined DN and OA treatment inhibited the expression of STAT3 and FAK, suppressing proliferation and the induction of pro-apoptotic protein expressions in A549 cells. Thus, a combination of DN and OA could be used as a therapeutical approach to malignant forms of lung cancer.