Numb had anti-tumor effects in prostatic cancer

Biomed Pharmacother. 2017 Aug:92:108-115. doi: 10.1016/j.biopha.2017.04.134. Epub 2017 May 19.

Abstract

Aim: The aim of this study was to explain the Numb anti-cancer effects in the prostatic cancer.

Methods: Collecting the 20 prostatic cancer patients and analyzing the correlation between Numb and Glease score. Transfection Numb into DU-145 and PC-3 cells, measuring the proliferation rate of difference groups by MTT assay, evaluating the cell apoptosis and cell cycle of difference group by Flow cytometry; measuring the invasion and migration abilities by transwell and wound healing assays. In the nude mice experiment, establish prostatic cancer nude mouse subcutaneous planting tumor model by DU-145 cells, Injection the Numb from tail vein. Evaluating the tumor volume and weight.

Results: The Numb protein expression was decreased with Glease score increasing. The proliferation rate of Numb groups were significantly decreased compared with NC groups (P<0.05, respectively). The apoptosis and G1 phase rates of Numb groups were significantly enhanced compared with NC groups (P<0.05, respectively). The invasion and migration abilities of Numb group cells were significantly weaken compared with NC groups (P<0.05, respectively). In the WB assay, The relative proteins (Numb, P53, Cyclin D1, Rac1, MMP-2 and MMP-9) expression were significantly differences between NC and Numb groups (P<0.05, respectively). In the vivo experiment, the tumor volume and weight of Numb group was significantly lighter than NC group (P<0.05, respectively).

Conclusion: Overexpression Numb had anti-cancer effects to prostatic cancer in vitro and vivo experiments, the mechanism might be P53/Cyclin D1 and Rac1/MMP-2/-9 signaling pathway.

Keywords: Cyclin D1; DU-145; MMP-2; MMP-9; Numb; P53; PC-3; Rac1.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • G1 Phase / drug effects
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Injections, Intravenous
  • Male
  • Membrane Proteins / administration & dosage
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / therapeutic use
  • Mice, Nude
  • Neoplasm Grading
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Proteins / administration & dosage
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / therapeutic use
  • Nerve Tissue Proteins / administration & dosage
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / therapeutic use
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / therapeutic use
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • NUMB protein, human
  • Recombinant Proteins