The Effect of Cridanimod on Progesterone Receptor Expression in EC
Cridanimod Efficiently Restores PrR Expression in Human PrR-negative EC Cell Lines but Do Not Affect the PrR Expression in Human PrR-positive EC Cell Lines
Tumors were established by IP injection of human endometrial cancer cells to athymic NCr-nu/nu mice and treated with medroxyprogesterone acetate (MPA) or combination of MPA and different doses of sodium cridanimod each other day starting D4 following xenotransplantation. PrRA and PrRB expression in tumors was analyzed by Western blot at D21.
Legend: C: Control; MPA: MPA alone; V1: MPA + Virexxa 1mg/mouse; V3: MPA + Virexxa 3mg/mouse; V6: MPA + Virexxa 6mg/mouse; Ad: -MPA and Adenovirus vectors bearing PR-A and PR-B receptor DNA
It is apparent that cridanimod do not affect PrR expression in PrR-positive human endometrial cell lines but trigger dose dependent increase of PrR expression in PrR-negative human endometrial cell lines.
Cridanimod- induced Restoration of PrR Expression in Combination with Progestin Therapy Generates Survival Benefit in Human PrR-negative EC Xenograft Models
PrR-negative tumors were established by IP injection of human Hec50co PrR-negative EC endometrial cancer cells to athymic NCr-nu/nu mice and treated with medroxyprogesterone acetate (MPA) or combination of MPA and different doses of sodium cridanimod each other day starting D4 following xenotransplantation.
The survival analysis by the Kaplan-Meier method has shown a significant difference among six groups. Multiple comparisons using the Holm-Sidak method indicate that the group receiving MPA plus sodium cridanimod at the dose of 6 mg has a significantly longer survival time than the control or MPA alone (62 ± 7.0 days vs. 38 ± 5 or 33 ± 3, respectively, p < 0.05). The group with MPA plus sodium cridanimod 3mg has a significantly longer survival than the group with MPA alone (56 ± 8.0 days vs. 33 ± 3, p < 0.05). The experimental findings suggest that addition of sodium cridanimod at the doses of 3mg and 6mg to a progestin treatment regimen has significantly improved survival of animals bearing advanced PrR-negative tumors.