Fig. 7
Progesterone enhanced the carbotaxol therapeutic effect on EC by inducing TRIM22 expression in vivo. (A) The TRIM22 putative progesterone responsive element (PRE) and the mutant site in the TRANSFAC database. (B) The Luciferase activity of TRIM22 and progesterone in Ishikawa cells. (C) ChIP detection of the association of PR with TRIM22 PRE in Ishikawa cells. (D) Statistical analysis of the association of PR with TRIM22 PRE in (C). (E) mRNA level of TRIM22 in Ishikawa cells treated with vehicle, MPA and MPA inhibitor RU486. (F) Immunoblots of TRIM22 in Ishikawa and KLE cells treated with vehicle and different concentration MPA. (G) Statistical analysis of TRIM22 in (F). (H) The CCK8 of Ishikawa and KLE cells treated with vehicle and different concentration MPA. (I) Representative images of pre-treatment and post-treatment IHC-stained (with an anti-TRIM22 antibody) sections of endometrial tissues from atypical endometrial hyperplasia (AEH) patients who accepted the high dose progesterone treatment for 3-6months. (J) Statistical analysis of TRIM22 in (I). (K) Statistical analysis of endometrial epithelium thickness in (I). (L) Statistical analysis of the ratio of endometrial glands to stroma in (I). (M) A subcutaneous tumor growth curve of xenograft mice treated with vehicle, carbotaxol, progesterone, combination progesterone and carbotaxol, combination progesterone, carbotaxol and IL-6R Ab at indicated time points (n = 5 mice per group). (N) Statistical analysis of last tumor volume in (M). (O) Statistical analysis of the last tumor weight of xenograft mice treated with vehicle, carbotaxol, progesterone, combination progesterone and carbotaxol, combination progesterone, carbotaxol and IL-6R Ab. (P) Representative H&E staining and IHC staining of Ki67 in xenograft tumors derived from (M). (Q) Statistical analysis of Ki67 expression in xenograft tumors derived from (M). (R)Statistical analysis of TRIM22 expression in xenograft tumors derived from (M). Data were expressed as means ± SEM of three independent experiments. Scale bar, 50 μm. *p < 0.05, **p < 0.01, ***p < 0.001