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Treatment of Endometrial Cancer Cell Lines with Telmisartan and VTP-27999 Reduces Cellular Proliferation and Viability (128394)

Tess L Symington 1 2 , Joshua J Fisher 3 4 , Paul Tooney 1 5 , Eugenie Lumbers 1 2 , Kirsty G Pringle 1 2
  1. School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, NSW, Australia
  2. Womens Health Research Program, Hunter Medical Research Institute, Newcastle, Australia
  3. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  4. Mothers and Babies Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia
  5. Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, Newcastle, Australia

Current treatments for endometrial cancer are not always effective, particularly for advanced or recurrent cases, and can have significant side effects. Our in silico analysis utilising The Broad Institute Drug Repurposing Hub database identified telmisartan, an angiotensin II type I receptor antagonist, and VTP-27999, a renin inhibitor, as medications that could be repurposed to reduce endometrial cancer cell viability in vitro. This study aimed to further examine the effect of telmisartan and VTP-27999 on endometrial cancer cell growth in vitro.

 

Endometrial cancer cell lines Ishikawa (Grade I), HEC1A (Grade II), and AN3CA (Grade III) were treated with 100uM of telmisartan or VTP-27999 (n=3/per cell line) for 48hrs in vitro. The SX5 Incucyte Live Cell Imager was used to measure cellular proliferation, cell viability was measured using the MTT assay. Scratch assays and trans-well invasion assays, alongside proteomic investigation, will also be performed.

 

Ishikawa cell proliferation was significantly reduced by 100uM telmisartan or VTP-27999 after 12hrs (p=0.027 and 0.009, respectively), persisting to 48 hrs of treatment (both p<0.0001). Treatment with 100uM VTP-27999 significantly decreased HEC1A proliferation after 36hrs (p<0.0001), persisting to 48hrs (p<0.0001). Proliferation of HEC1A cells was also decreased at 48hrs with 100uM telmisartan (p=0.003, and p=0.0135, respectively). AN3CA cellular proliferation was significantly decreased with 100uM telmisartan or VTP-27999 treatment for 12hrs (p=0.017, and p=0.005, respectively), continuing to 48hrs (p=0.005 and p=0.011, respectively). Cell viability was significantly decreased in Ishikawa and AN3CA cell lines after 48hr treatment with 100uM telmisartan or VTP-27999 (Ishikawa: p=0.006 and p=0.017, AN3CA: both p<0.0001). HEC1A cell viability did not change with either treatment.

 

Both telmisartan and VTP-27999 slowed the proliferation of all endometrial cancer cell lines and decreased the cellular viability of Ishikawa and AN3CA cells. Therefore, telmisartan and VTP-27999 show strong potential to be repurposed for endometrial cancer treatment and to improve clinical outcomes.