J Cancer 2017; 8(10):1917-1926. doi:10.7150/jca.18040
Fluorofenidone Inhibits the Proliferation of Lung Adenocarcinoma Cells
1. Department of pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
2. Department of pathology, School of basic medicine, Central South University, Changsha, Hunan, 410078, China
3. Department of pulmonary Medicine, XiangYa Hospital, Central South University, Changsha, Hunan, 410008, China
4. Department of Nephropathy, XiangYa Hospital, Central South University, Changsha, Hunan, 410008, China
5. Faculty of Pharmaceutical Sciences, Central South University, Changsha Hunan 410013, China
6. State Key Laboratory of Medical Genetics of China, Changsha, Hunan 410078, China
Background: Lung carcinoma is the leading cause of malignant tumor related mortality in China in recent decades, and the development of new and effective therapies for patients with advanced lung carcinoma is needed. We recently found that fluorofenidone (FD), a newly developed pyridine compound, reduced the activation of Stat3 (Signal transducer and activator of transcription 3) in fibroblasts. Stat3 plays a crucial role in the development of lung cancer and may represent a new therapeutic target. In this study, we examined the effect of FD on human lung adenocarcinoma cells in vivo and in vitro.
Methods: The effect of FD on the growth of lung cancer cells was measured with a CCK-8 assay, colony formation assay and xenograft tumor model. A flow cytometry analysis was performed to study cell cycle arrest and apoptosis. Western blotting and immunohistochemistry were used to observe the expression of Stat3. Changes in the expression of RNA induced by FD were assessed using gene chip and real-time RT-PCR assays.
Results: In vitro, FD inhibited the growth of lung adenocarcinoma A549 and SPC-A1 cells in a dose-dependent manner. After treatment with FD, the A549 and SPC-A1 cells were arrested in the G1 phase, and apoptosis was induced. In vivo, this compound significantly inhibited the growth of tumors that were subcutaneously implanted in mice. Moreover, FD decreased Stat3 activity in lung cancer cells and xenograft tumor tissue, and microarray chip results showed that FD altered the gene expression profile of lung cancer cells. Specifically, NUPR1, which plays a significant role in cancer development, was down-regulated by FD in lung cancer cells.
Conclusion: Our study supports the clinical evaluation of FD as a potential lung adenocarcinoma therapy.
Keywords: Fluorofenidone, lung adenocarcinoma, Stat3, NUPR1.
Deng Zh, Meng J, Tang J, Hu Gy, Tao Lj. Fluorofenidone Inhibits the Proliferation of Lung Adenocarcinoma Cells. J Cancer 2017; 8(10):1917-1926. doi:10.7150/jca.18040. Available from http://www.jcancer.org/v08p1917.htm