Proteomic analysis of VTP-27999 and telmisartan treated endometrial cancer cells <em>in vitro</em> — ASN Events
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  3. Proteomic analysis of VTP-27999 and telmisartan treated endometrial cancer cells in vitro

Proteomic analysis of VTP-27999 and telmisartan treated endometrial cancer cells in vitro (#528)

Tess L Symington 1 2 , Joshua J Fisher 2 3 , Heather C Murray 1 4 , Paul Tooney 1 5 , Eugenie R Lumbers 1 2 , Kirsty G Pringle 1 2
  1. School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, NSW, Australia
  2. Reproductive and Family Health Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia
  3. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  4. Precision Medicine Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia
  5. Mark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Newcastle, NSW, Australia

Background:

Globally, endometrial cancer is one of the only cancers with an increasing incidence and mortality rate. Within Australia, incidence rates are rising fastest between ages 25-44. This highlights the need for newer treatments, especially to preserve fertility as hysterectomy is the most common treatment. We have previously shown the anti-hypertensives VTP-27999 and telmisartan are effective at reducing endometrial cancer cell proliferation and viability in vitro. This study aimed to assess changes to the proteome of grade I endometrial cancer cells (Ishikawa) treated with VTP-27999 and telmisartan.

 

Methods:

Ishikawa cells were left to attach for 24h before being treated with VTP-27999 or telmisartan at 50 or 100 mM, or with vehicle control (n=3). Following 24h of treatment, cells were collected for proteomic assessment by liquid chromatography-mass spectrometry (LC-MS).

 

Results:

Compared to VTP-2799, telmisartan caused a greater number of proteins to be significantly altered (28 or 112 significantly downregulated, 30 or 33 significantly upregulated following 50 or 100 mM treatment respectively). In comparison, VTP-27999 treatment resulted in the significant downregulation of nine proteins and significant upregulation of up to ten proteins with 50 or 100 mM treatment. This was the first study to suggest that VTP-27999, much like telmisartan, has PPAR-gamma agonist like effects through the significant upregulation of PPAR-associated proteins including ATOC8, NCOA4 and LPIN3. LC-MS identified changes to proteins involved in PI3K and PTEN pathways, however Ingenuity Pathway Analysis only identified a significant decrease in pathways of ‘Cell proliferation of tumor cell lines’ and pathways involved in cell movement with telmisartan treatment, suggesting VTP-27999 was only partially effective at inhibiting proliferation.

 

Conclusion:

There is now comprehensive evidence to further explore the use of VTP-27999 and telmisartan as effective treatments of endometrial cancer, especially to help preserve fertility in patients and give them the best reproductive capacity in life.