The role of GDF15 in bone metastasis of lung adenocarcinoma cells

Duan,Lian; Pang,Hai‑Lin; Chen,Wen‑Jun; Shen,Wei‑Wei; Cao,Pei‑Pei; Wang,Shu‑Mei; Liu,Li‑Li; Zhang,He‑Long

doi:10.3892/or.2019.7024

The role of GDF15 in bone metastasis of lung adenocarcinoma cells

Authors:
- Lian Duan
- Hai‑Lin Pang
- Wen‑Jun Chen
- Wei‑Wei Shen
- Pei‑Pei Cao
- Shu‑Mei Wang
- Li‑Li Liu
- He‑Long Zhang
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Affiliations: Department of Oncology, Tangdu Hospital, The Air Force Medical University, Xi'an, Shaanxi 710038, P.R. China, Department of Pathology, Tangdu Hospital, The Air Force Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: February 21, 2019 https://doi.org/10.3892/or.2019.7024
Pages: 2379-2388

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Abstract

Lung cancer is the most common malignant tumor in China. It often metastasizes to bone, thereby significantly shortening the lives of patients, and reducing their quality of life. However, the efficacy of treatment for bone metastasis of lung cancer at this stage is very limited. The development and clinical application of molecular‑targeted drugs for the effective targeted therapy of bone metastasis of lung cancer are urgently required. The growth differentiation factor 15 (GDF15) gene which may be associated with bone metastasis of lung cancer, was screened out by whole‑genome sequencing. In the present study, we used a recombinant GDF15 lentivirus technique to upregulate the expression of GDF15 in lung adenocarcinoma A549 cells, and the results revealed that GDF15 could inhibit the proliferation, migration and invasion, while promoting apoptosis of A549 cells. In addition, GDF15 significantly decreased the number and sites of lung metastases and bone metastases in vivo compared to the control group. Finally, it was revealed that Smad2 and phospho‑Smad2 protein expression was lower in the GDF15‑overexpressing A549 cells. This result indicated that the tumor suppressive effect of GDF15 may be related to the TGF‑β/Smad signaling pathway, although more studies are still required for confirmation. In summary, GDF15 inhibited the growth and bone metastasis of lung adenocarcinoma A549 cells, and this effect may be achieved through the TGF‑β/Smad signaling pathway.

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