Effects of gestrinone on uterine leiomyoma and expression of c-Src in a guinea pig model

Abstract

Aim: To investigate the effect of gestrinone on uterine leiomyomas and the expression of c-Src, estradiol receptors (ER), and progesterone receptors (PR) in a guinea pig model. Methods: After being oophorectomized, the guinea pigs were allocated into random groups. The model group was treated with estradiol benzoate (E 2 ) for 16 weeks. In the gestrinone-treated groups, the animals were treated with E 2 for 6 weeks in advance, and then in combination with gestrinone for 10 weeks. Histological examination was performed to evaluate whether there were leiomyoma features in the animals. The protein levels of c-Src, phospho-416 Src, ER, and PR were assayed by Western blotting and an immunohistochemical method. Results: Morphological changes were observed in the myometrium of the guinea pig model, including an increase of uterine weights, proliferation of uterine smooth muscles, and the formation of nodules. High protein levels of c-Src, phospho-416 Src, ER, and PR were observed in the myometrium of the guinea pig model. In the gestrinone-treated group, there were no nodules observed. The histological features of the myometrium were similar to that of the control group. Low protein levels of c-Src, phospho-416 Src, ER, and PR were observed in the gestrinonetreated group. Conclusion: The upregulation of c-Src and phospho-416 Src indicated that the activity of c-Src is augmented in the uterine leiomyoma model. c-Src was associated with the formation of uterine leiomyomas in the model, and gestrinone markedly suppressed the growth of uterine leiomyomas in the model. Gestrinone inhibited not only the protein expression of ER and PR, but also c-Src and the autophosphorylation of c-Src in the guinea pig leiomyoma model.

Ginsenoside Rh2 suppresses growth of uterine leiomyoma in vitro and in vivo and may regulate ERα/c-Src/p38 MAPK activity

“…Histologically, proliferative features were demonstrated, similar to the morphology observed in guinea pigs (Zhu et al, 2007). After treatment with Rh2, the relative uterine weight decreased and body weight increased in a dose-dependent manner.…”

“…Similar to gestrinone and gossypol, the mechanism of action of Rh2 involves regulating the activities of ERα/c-Src/p38 MAPK. First, we established an animal model of ULs by injecting oophorectomized rats subcutaneously with E2 and P4 (Fujii et al, 1981;Zhu et al, 2007). We did not utilize Eker rats because Eker rat tumours are dependent on E2 but not P4.…”

“…The models of ULs were established according to Fujii et al (1981) and Zhu et al (2007) with some modifications. Fortyeight female SD rats were randomly divided into six groups.…”

“…Here, we investigated the impact of Rh2 on UL growth in vitro and in vivo. Because activation of c-Src and p38 MAPK were reported to contribute to the growth of ULs (Zhu et al, 2007(Zhu et al, , 2010(Zhu et al, , 2012, we further investigated the effect of Rh2 on several signalling molecules, including oestrogen receptor alpha (ERα), c-Src, and p38 MAPK.…”

Involvement of Bcl-2, Src, and ERα in gossypol-mediated growth inhibition and apoptosis in human uterine leiomyoma and myometrial cells

“…Overexpression and aberrant activation of c-Src have been found in a variety of epithelial and non-epithelial cancers [11,12] . We demonstrated that c-Src was also over-expressed in a guinea pig model of uterine leiomyoma induced by estradiol [13] . This evidence suggests that Src may be involved in the development of leiomyoma.…”