New therapeutic schedule for prostatic cancer-3 cells with ET-1 RNAi and Endostar

Asian Pac J Cancer Prev. 2014;15(23):10079-83. doi: 10.7314/apjcp.2014.15.23.10079.

Abstract

Background: Endothelin-1 and Endostar are both significant for the progression, proliferation, metastasis and invasion of cancer. In this paper, we studied the effect of ET-1 RNAi and Endostar in PC-3 prostatic cancer cells.

Materials and methods: The lentiviral vector was used in the establishment of ET-1 knockdown PC-3 cells. Progression and apoptosis were assessed by CKK-8 and flow cytometry, respectively. Transwell assay was used to estimate invasion and signaling pathways were studied by Western blotting.

Results: ET-1 mRNA and protein in ET-1 knockdown PC-3 cells were reduced to 26.4% and 22.4% compared with control group, respectively. ET-1 RNAi and Endostar both were effective for the suppression of progression and invasion of PC-3 cells. From Western blotting results, the effects of ET-1 regulation and Endostar on PC-3 cells were at least related to some signaling pathways involving PI3K/Akt/Caspase-3, Erk1/2/Bcl-2/Caspase-3 and MMPs (MMP-2 and MMP-9). Furthermore, combined treatment of ET-1RNAi and Endostar was found to be more effective than single treatment.

Conclusions: Both ET-1 RNAi and Endostar can inhibit the progression and invasion of PC-3 cells, but combined treatment might be a better therapeutic schedule.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Caspase 3 / drug effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • Endostatins / pharmacology*
  • Endothelin-1 / genetics*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / drug effects
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / pharmacology*
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Endostatins
  • Endothelin-1
  • RNA, Messenger
  • RNA, Small Interfering
  • Recombinant Proteins
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • CASP3 protein, human
  • Caspase 3
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • endostar protein