2. Academic Validation
  3. Anlotinib prove to be a potential therapy for the treatment of pulmonary fibrosis complicated with lung adenocarcinoma

Anlotinib prove to be a potential therapy for the treatment of pulmonary fibrosis complicated with lung adenocarcinoma

  • Pulm Pharmacol Ther. 2023 Mar 9;102202. doi: 10.1016/j.pupt.2023.102202.
Shanshan Chen 1,  Dandi Gao 2,  Ronghao Sun 3,  Jiali Bao 4,  Chunya Lu 5,  Zihui Zhang 6,  Ting Xiao 7,  Xiaoting Gu 8,  Honggang Zhou 9
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Zhengzhou University, 1 Longhu Middle Ring Road, Zhengzhou, Jinshui District, Henan Province, People's Republic of China. Electronic address: chenshancs82@163.com.
  • 2 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: 2120201198@mail.nankai.edu.cn.
  • 3 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: 2120201186@mail.nankai.edu.cn.
  • 4 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: baojiali20@163.com.
  • 5 The First Affiliated Hospital of Zhengzhou University, 1 Longhu Middle Ring Road, Zhengzhou, Jinshui District, Henan Province, People's Republic of China.
  • 6 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China.
  • 7 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: tingxiao@nankai.edu.cn.
  • 8 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: guxiaoting320@126.com.
  • 9 State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin, 300353, People's Republic of China. Electronic address: honggang.zhou@nankai.edu.cn.
PMID: 36906117 DOI: 10.1016/j.pupt.2023.102202
Abstract

Pulmonary fibrosis is a chronic interstitial fibrosis lung disease with high mortality, which is often complicated with lung Cancer. The incidence of IPF complicated with lung Cancer is getting higher and higher. At present, there is no consensus on the management and treatment of pulmonary fibrosis patients with lung Cancer. There is an urgent need to develop preclinical drug evaluation methods for IPF with lung Cancer and potential therapeutic drugs for IPF with lung Cancer. The pathogenic mechanism of IPF is similar to that of lung Cancer, and the multi-effect drugs with Anticancer and anti-fibrosis will have potential value in the treatment of IPF complicated with lung Cancer. In this study, we established an animal model of IPF complicated with lung Cancer in situ to evaluate the therapeutic effect of the antiangiogenic drug anlotinib. The pharmacodynamic results in vivo showed that anlotinib could significantly improve the lung function of IPF-LC mice, reduce the content of collagen in lung tissue, increase the survival rate of mice, and inhibit the growth of lung tumor in mice. The results of Western blot and immunohistochemical analysis of lung tissue showed that anlotinib significantly inhibited the expression of fibrosis marker protein α-SMA, Collagen I and Fibronectin and tumor proliferation marker protein PCNA in mouse lung tissue, and down-regulated the content of serum tumor marker CEA. Through transcriptome analysis, we found that anlotinib regulates MAPK signal pathway, PARP signal pathway and coagulation cascade signal pathway in lung Cancer and pulmonary fibrosis, which all play an important role in lung Cancer and pulmonary fibrosis. In addition, there is crosstalk between the signal pathway participated by the target of anlotinib and MAPK, JAK/STAT and mTOR signal pathway. In summary, anlotinib will be a candidate for IPF-LC treatment.

Keywords

Anlotinib; Idiopathic pulmonary fibrosis; Lung cancer.

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