Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (3): 458-463.doi: 10.3969/j.issn.2095-4344.0578

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Effects of recombinant human bone morphogenetic protein-2 on the proliferation of breast cancer MCF-7 cells

Liu Shuzhong1, Lao Lifeng2   

  1.  (1Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Orthopedics, Peking Union Medical College Hospital, Beijing 100730, China; 2Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China)
  • Received:2018-07-08 Online:2019-01-28 Published:2021-04-28
  • Contact: Lao Lifeng, MD, Attending physician, Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • About author:Liu Shuzhong, MD, Physician, Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Orthopedics, Peking Union Medical College Hospital, Beijing 100730, China
  • Supported by:

    the Medicine-Guided Science and Technology Project of Shanghai Science and Technology Commission, No. 17411964200 (to LLF); the Talent Program of Shanghai Pujiang, No. 15PJD026 (to LLF); the Medical-Engineering Joint Foundation of Shanghai Jiao Tong University, No. YG2014MS51 (to LLF); the Clinical Research and Innovation Foundation of Renji Hospital of Shanghai, No. PYXJS16-006 (to LLF)

Abstract:

BACKGROUND: Clinical application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been found to increase the risk for malignant tumors, but the effect of rhBMP-2 on the proliferation of breast cancer MCF-7 cells and the underlying mechanism remain unclear.
OBJECTIVE: To explore the effects of rhBMP-2 on the proliferation of breast cancer MCF-7 cells and the underlying mechanism in vivo and in vitro.
METHODS: In vitro study: cell proliferation of MCF-7 under different concentrations of rhBMP-2 was determined by MTT assay and flow cytometry in serum-free condition. The cell cycle was detected by flow cytometry. The expression levels of p21 and cyclin E were detected by real-time PCR. The protein levels of p21, cyclin E and phosphorylation of PI3K/Akt were tested by western blot and real-time PCR. In vivo study: fourteen 6-week-old female nude mice were divided into two groups: experimental group (subcutaneous injection of rhBMP-2 plus MCF-7 cells), control group (subcutaneous injection of the same volume of MCF-7 cells).
RESULTS AND CONCLUSION: In vitro study: rhBMP-2 markedly inhibited the proliferation of MCF-7 cells in serum-free condition. After 24-hour treatment, rhBMP-2 could increase the G1 cell ratio. rhBMP-2 could significantly increase the expression of p21 as well as significantly inhibit the expression of cyclin E and phosphorylation in the PI3K/Akt signaling pathway. In vivo study: the volume of subcutaneous tumor in the experimental group was smaller than that in the control group. Immunohistochemistry revealed that rhBMP-2 could significantly decrease the expression level of ki-67 in tumor tissues. Our study suggests that rhBMP-2 has significantly suppressive effect on the proliferation of breast cancer MCF-7 cells via PI3K/Akt pathway in vitro and in vivo. Therefore, we can provide the basic science data to avoid risks of breast cancer and to support the utilization of rhBMP-2 in the management of spinal fusion, treatment of bone ununion and other orthopedic disorders.

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松组织工程

Key words: Bone Morphogenetic Proteins, Neoplasms, Cell Proliferation, Tissue Engineering

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