search button
Open Access

The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging

  • Authors:
    • Shengfei Wang
    • Xiaomin Niu
    • Xiao Bao
    • Qin Wang
    • Jianping Zhang
    • Shun Lu
    • Yongjun Wang
    • Ling Xu
    • Mingwei Wang
    • Jie Zhang

  • View Affiliations

  • Published online on: March 20, 2019     https://doi.org/10.3892/or.2019.7080
  • Pages: 2636-2646

  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Non‑small cell lung cancer (NSCLC) metastasis commonly occurs in bone, which often results in pathological fractures. Sustained phosphoinositide‑3‑kinase (PI3K) signalling promotes the growth of PI3K‑dependent NSCLC and elevates osteoclastogenic potential. The present study investigated the effects of a PI3K inhibitor on NSCLC growth in bone and osteoclast formation, and aimed to determine whether it could control symptoms associated with bone metastasis. A bone metastasis xenograft model was established by implanting NCI‑H460‑luc2 lung cancer cells, which contain a phosphatidylinositol‑​4,5‑bisphosphate 3‑kinase catalytic subunit α mutation, into the right tibiae of mice. After 1 week, the tumours were challenged with a PI3K inhibitor (buparlisib) or blank control for 3 weeks. Tumour growth and burden were longitudinally assessed in vivo via reporter gene bioluminescence imaging (BLI), small animal positron emission tomography/computed tomography (CT) [18F‑fluorodeoxyglucose (18F‑FDG)] and single‑photon emission computed tomography/CT [99mTc‑methylene diphosphonate (99mTc‑MDP)] imaging. Tibia sections of intraosseous NCI‑H460 tumours were analysed by immunohistochemistry (IHC), western blotting and flow cytometry. Dynamic weight bearing (DWB) tests were further performed to examine the improvement of symptoms associated with bone metastasis during the entire study. Administration of buparlisib significantly inhibited the progression of bone metastasis of NSCLC, as evidenced by significantly reduced uptake of 18F‑FDG, 99mTc‑MDP and BLI signals in the treated lesions. In addition, buparlisib appeared to inhibit the expression of tartrate‑resistant acid phosphatase and receptor activator of nuclear factor‑κB ligand, as determined by IHC. Buparlisib also resulted in increased cell apoptosis, as determined by a higher percentage of Annexin V staining and increased caspase 3 expression. Furthermore, buparlisib significantly increased weight‑bearing capacity, as revealed by DWB tests. The PI3K inhibitor, buparlisib, suppressed osteoclast formation in vivo, and exhibited antitumour activity, thus leading to increased weight‑bearing ability in mice with bone metastasis of lung cancer. Therefore, targeting the PI3K pathway may be a potential therapeutic strategy that prevents the structural skeletal damage associated with bone metastasis of lung cancer.
View Figures
View References

Related Articles

Journal Cover

May-2019
Volume 41 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

  • Journal Metrics
  • Impact Factor: 4.2
  • Ranked Oncology
    (total number of cites)
  • CiteScore: 8.4
  • CiteScore Rank: Q1: #68/366 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.786
  • SCImago Journal Rank (SJR): 0.812
International Symposium on Molecular Medicine Conference Banner
The Cancer Story
World Congress on Advances in Oncology and International Symposium on Molecular Medicine Conference Banner
World Academy Of Sciences Banner
Heyday Road Banner

0

Copy and paste a formatted citation
x
Spandidos Publications style
Wang S, Niu X, Bao X, Wang Q, Zhang J, Lu S, Wang Y, Xu L, Wang M, Zhang J, Zhang J, et al: The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging. Oncol Rep 41: 2636-2646, 2019
APA
Wang, S., Niu, X., Bao, X., Wang, Q., Zhang, J., Lu, S. ... Zhang, J. (2019). The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging. Oncology Reports, 41, 2636-2646. https://doi.org/10.3892/or.2019.7080
MLA
Wang, S., Niu, X., Bao, X., Wang, Q., Zhang, J., Lu, S., Wang, Y., Xu, L., Wang, M., Zhang, J."The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging". Oncology Reports 41.5 (2019): 2636-2646.
Chicago
Wang, S., Niu, X., Bao, X., Wang, Q., Zhang, J., Lu, S., Wang, Y., Xu, L., Wang, M., Zhang, J."The PI3K inhibitor buparlisib suppresses osteoclast formation and tumour cell growth in bone metastasis of lung cancer, as evidenced by multimodality molecular imaging". Oncology Reports 41, no. 5 (2019): 2636-2646. https://doi.org/10.3892/or.2019.7080