Therapeutic effects of sorafenib on the A549/DDP human lung adenocarcinoma cell line in vitro

Abstract

The aim of the present study was to observe the effects of sorafenib on the proliferation, apoptosis and invasion of A549/DDP cisplatin-resistant lung adenocarcinoma cells cultured in vitro. The A549/DDP cisplatin-resistant lung adenocarcinoma cell strain was cultured in vitro, the cell culture group incubated in culture medium only was set as the control group (Group S0) and the four concentration gradients of sorafenib were added to the culture groups as the experimental groups: S1, 2 µmol/l; S2, 4 µmol/l; S3, 8 µmol/l; and S4, 16 µmol/l. The MTT assay was used to determine the growth inhibition rate of the cells, which were respectively subjected to sorafenib treatment for 24, 48 and 72 h. Flow cytometry was used to determine the rate of apoptosis of cells in each group following sorafenib treatment for 72 h. Furthermore, the Transwell invasion experiment was used to determine the effect on A549/DDP cell invasion following sorafenib treatment for 24 h. Based on the MTT assay, it was found that the inhibition rates of A549/DDP cisplatin-resistant lung adenocarcinoma cells in groups S1-4 following sorafenib treatment for 24 h were 4.58±2.82, 14.93±2.62, 37.58±7.13 and 58.39±8.15%, respectively. For 48 h, inhibition rates in S1-4 were 14.98±2.93, 26.28±7.31, 63.00±3.05 and 78.84±3.96%, respectively, and for 72 h, inhibition rates were 18.80±2.82, 32.71±2.55, 75.51±4.73 and 87.50±3.36%, respectively. The difference in the inhibition rates of cells among the experimental groups for the same incubation time showed statistical significance (P<0.05). Flow cytometric analysis indicated that the rate of apoptosis in the control group was 8.88±0.81% following sorafenib treatment for 72 h, and the rates of apoptosis in groups S1-4 were, 12.84±0.24, 17.27±0.78, 21.98±0.75 and 49.67±1.38%, respectively. The rate of apoptosis in each experimental group was higher compared with that in the control group (P<0.05). The difference in the rate of apoptosis among the experimental groups was statistically significant (P<0.05). The Transwell assay showed that the number of cells permeating the septum in the control group was 82.7±2.3/high power lens (HP), while the average number of cells permeating septum in groups S1-4 following treatment with sorafenib for 24 h was 58.2±2.5, 41.3±1.3, 22.6±2.1 and 14.7±1.1/HP, which was significantly lower compared with the control group. The number of cells permeating the septum in each experimental group decreased with the enhancement of the concentration gradient. The differences were statistically significant (P<0.05). In conclusion, sorafenib inhibits the proliferation of A549/DDP cisplatin‑resistant lung adenocarcinoma cells in a time‑ and concentration‑dependent manner. In addition, sorafenib induces apoptosis in A549/DDP cisplatin‑resistant lung adenocarcinoma cells, thus reducing their invasiveness.

Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries

“…Sorafenib (NEXAVAR; SOR) is a multi-target protein kinase inhibitor approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma [ 39 , 40 ]. Although SOR has not been approved for lung cancer, it is still the subject of extensive research related to lung cancer [ 41 , 42 , 43 ]. Results of the retrospective analysis reported that SOR significantly prolongs the recurrence-free survival of cancer patients.…”

“…It also demonstrated that SOR in combination with antitumor mesenchymal stem cells potently inhibited tumor growth and preserved the antitumor-associated anti-inflammatory effects of mesenchymal stem cells [ 46 ]. Although previous studies suggested the efficacy of SOR against lung cancer [ 41 , 43 ] to the best of our knowledge, there is no study evaluating the relationship between JNK and COX-2 signaling and SOX-2 in the lung premalignant microenvironment. Therefore, we aimed to determine the mechanistic effect of SOR in DEN-induced lung carcinogenesis using a rat model.…”