If IC/BPS patients present increased expression of VEGF in the bladder, agents which affect VEGF or VEGR would have therapeutic effect. Axitinib is a tyrosine kinase inhibitor which is assumed to primarily act on VEGF receptor (VEGFR) 1 -3 and platelet-derived growth factor receptor (PDGFR), and inhibits angiogenesis and cell proliferation. Axitinib is currently indicated for the treatment of advanced renal cell carcinoma. In this present study, we initially  investigated the therapeutic effects of axitinib in HCl-induced interstitial cystitis rat model. Then, we examined the bladder tissues of IC/BPS patients to identify the expression of VEGF, VEGFR, PDGF and PDGFR.

10-week-old female Sprague Dawley rats were divided into three groups: Sham (n=10), HCl group (n=10), and HCl + axitinib group (n=10). Interstitial cystitis was induced with intravesical instillation of 0.2M HCl for 10 minutes followed by washing with saline. Phosphate-buffered saline was used instead of HCl in sham group. One week after instillation (Day 0), HCl+Axitinib group received oral administration of axitinib (1mg/kg) for consecutive five days with two-day rest period. During axitinib administration, von-frey test was performed daily for pain evaluation (Day 1 to Day 5). On Day 7, awake cystomerty was performed and bladder was harvested for histological and genetic expression analysis. 
After the evaluation of therapeutic effects of Bladder tissues of 15 patients (Hunner-type IC : non-Hunner type IC : Control, n=5, respectively) were stained with VEGF, VEGFR-2, PDGF and PDGFR-2. The histological examination was performed by a single urological pathologist who were blinded to the clinical information.

Pain threshold improved significantly three days after axitinib administration in HCl+axitinib group. On awake cystometry, voiding dysfunction was improved by decreased non-voiding contraction, increased micturition interval and micturition volume by axitinib. On histological analysis, urothelial denudation, mast cell infiltration and fibrosis was alleviated and angiogenesis was inhibited in HCl+axitinib group. HCl instillation increased expression of tyrosin kinase receptors including platelet-derived growth factor (PDGF), PDGF receptor (PDGF-R), vascular endothelial growth factor (VEGF) and VEGF receptor (VEGF-R) while peroral axinitib administration inhibited subtypes of PDGF, PDGF-R, VEGF and VEGF-R. 
In addition, bladder tisuse of IC patients had more prominent expression of VEGF than normal healthy controls.

Various mechanisms have been suggested to explain the pathogenesis of IC - mast cell activation, gag layer damage, potassium hypersensitivity, and autoimmunity, but pathophysiology of the disease is yet to be determined. IC/BPS is chronic inflammatory disease which is considered to be loco-extensive and affect the whole bladder. Studies have reported that bladder tissue of IC/BPS patients presented significantly higher expression of VEGF (vascular endothelial growth factor) resulting in increased immature angiogenesis. VEGF is important in maintaining tight cell junction and bladder permeability, and it is also distributed at bladder vessel, apical cell and intramural ganglia. Moreover, Hunner lesion is classically defined as “a circumscript, reddened mucosal area with small vessels radiating towards a central scar with or without coagulum". It can be assumed that abnormal vessels might play some role pathogenesis of interstitial cystitis. The findins of this preclinical study suggest that axitinib might play potential  therapeutic role in treating IC.

Oral administration of axitinib improved pain, voiding profiles and urothelial integrity by inhibiting angiogenesis in interstitial cystitis in rat model. Moreover, bladder tissue of IC patients had more evident expression of VEGF than healthy control.