Tumor Biology

, Volume 35, Issue 6, pp 5189–5198 | Cite as

Bone morphogenetic protein 2 inhibits hepatocellular carcinoma growth and migration through downregulation of the PI3K/AKT pathway

  • Ying Zheng
  • Xuemei Wang
  • Haidong Wang
  • Wei Yan
  • Quan Zhang
  • Xin Chang
Research Article


Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Previous studies have suggested that abnormal expression of BMP-4, BMP-7, and BMP-9 is correlated with tumor progression in HCC, but the role played by BMP-2 in HCC has not yet been reported. To determine the role of BMP-2 in HCC, we first investigated the effect of exogenous BMP-2 on the growth of the cell lines HCC SK-Hep-1, Hep G2, and Hep 3B. Next, we studied the function of BMP-2 in SK-Hep-1 HCC cell line using a recombinant lentivirus vector to deliver BMP-2. We also used siRNA to silence endogenous BMP-2 expression in the HCC Hep 3B cell line. Then, cell growth and migration were assayed in vitro using WST-8, wound-healing, and transwell invasion assays. Cellular apoptosis and cell-cycle distribution were assessed using flow cytometry. We also investigated the effects of BMP-2 overexpression and knockdown on the expression of proliferating cell nuclear antigen (PCNA), matrix metallopeptidase-2 (MMP-2), phosphorylated AKT (p-AKT), phosphoinositide 3-kinase p85α (PI3Kp85α), Bax, Bcl-2, caspase-3, cleaved caspase-3, p21, and cyclin E. As a result, we observed that BMP-2 inhibited the proliferation of HCC cells. Furthermore, HCC cell proliferation and migration were significantly diminished by BMP-2 overexpression, as was indicated by WST-8, would healing, and transwell assays, while knockdown of BMP-2 led to an increase in proliferation and migration of Hep 3B cells. BMP-2 overexpression significantly increased the susceptibility of SK-Hep-1 cells to low-serum-induced apoptosis, while BMP-2 knockdown reduced the susceptibility of Hep 3B cells. Overexpression of BMP-2 induced G1 phase arrest through upregulation of p21. When BMP-2 expression was elevated in SK-Hep-1 cells, the expression of PI3Kp85α, p-AKT, PCNA, and MMP-2 declined. These results suggest that BMP-2 exerts an inhibitory effect on the growth and migration of HCC cells, possibly via a blockade of PI3K/AKT signaling.


Bone morphogenetic protein 2 Hepatocellular carcinoma Migration PI3K AKT 


Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ying Zheng
    • 1
  • Xuemei Wang
    • 2
  • Haidong Wang
    • 3
  • Wei Yan
    • 4
  • Quan Zhang
    • 5
  • Xin Chang
    • 6
  1. 1.Department of AnesthesiaHuai’an First People’s Hospital, Nanjing Medical UniversityHuai’anPeople’s Republic of China
  2. 2.Department of UltrasoundObstetrics and Gynecology Hospital of Fudan UniversityShanghaiPeople’s Republic of China
  3. 3.Department of Obstetrics and GynecologyHuai’an First People’s Hospital, Nanjing Medical UniversityHuai’anPeople’s Republic of China
  4. 4.Department of GastroenterologyHuai’an First People’s Hospital, Nanjing Medical UniversityHuai’anPeople’s Republic of China
  5. 5.Department of OncologyHuai’an First People’s Hospital, Nanjing Medical UniversityHuai’anPeople’s Republic of China
  6. 6.Department of Imaging Medicine CenterHuai’an First People’s Hospital, Nanjing Medical UniversityHuai’anPeople’s Republic of China

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