Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease of unknown etiology. At present, the mortality rate of the deadly disease is still very high, while the existing treatments only delay the progression of the disease and improve the quality of life of patients. Lung cancer (LC) is the most fatal disease in the world. In recent years, IPF has been considered to be an independent risk factor for the development of LC. The incidence of lung cancer is increased in the patients with IPF and the mortality is also significantly increased in the patients inflicted with the two diseases. In this study, we evaluated an animal model of pulmonary fibrosis complicated with LC by implanting LC cells orthotopically into the lungs of mice several days after bleomycin induction of the pulmonary fibrosis in the same mice. In vivo studies with the model showed that exogenous recombinant human thymosin beta 4 (exo-rhT beta 4) alleviated the impairment of lung function and severity of damage of the alveolar structure by the pulmonary fibrosis and inhibited the proliferation of LC tumor growth. In addition, in vitro studies showed that exo-rhT beta 4 inhibited the proliferation and migration of A549 and Mlg cells. Furthermore, our results also showed that rhT beta 4 could effectively inhibit the JAK2-STAT3 signaling pathway and this might exert an anti-IPF-LC effect. The establishment of the IPF-LC animal model will be helpful for the development of drugs for the treatment of IPF-LC. Exogenous rhT beta 4 can be potentially used for the treatment of IPF and LC.

Automated summary

In this study, an animal model of pulmonary fibrosis complicated with lung cancer was evaluated. It was found that exogenous recombinant human thymosin beta 4 (exo-rhT beta 4) can alleviate the impairment caused by pulmonary fibrosis, inhibit the growth of lung cancer tumor cells, and effectively inhibit the JAK2-STAT3 signaling pathway. The establishment of the IPF-LC animal model is helpful for drug development and exogenous rhT beta 4 shows potential for the treatment of IPF and LC.