Inhibition of JAK3/STAT3 Activation in Rats Uterine Leiomyoma by formula of Taohong Siwu Decoction: A Randomized Controlled Trial

Abstract Background: Traditional Chinese medicine (TCM) formula of Taohong Siwu decoction (THSW) is often used in traditional Chinese medicine for the treatment of uterine leiomyoma (UL). The effectiveness of THSW for the treatment of UL has been confirmed in previous studies. At present, there are few relevant mechanism studies. The purpose of this study is to explore the efficacy and mechanism of THSW in the treatment of uterine leiomyoma. Methods: A Sprague Dawley (SD) rat model of UL was established via estrogen and progesterone load combined with external stimulation for 5 weeks. We randomly assigned adult female non-pregnant rats into six groups: a control group, a UL model group, and a positive drug group, THSW(18g/ml) group, THSW(9g/ml) group, THSW(4.5g/ml) group. THSW group and positive drug group were treated with THSW medicinal solutions and gongliuxiao capsule medicinal solutions respectively after daily modeling for 3 weeks. Histological analyses, Polymerase Chain Reaction and western blotting were performed to evaluate the effect of THSW on UL and elucidate its mechanism of action. Results: The uterus morphology of the model group showed significantly more swelling than that of the control group, and pathological of changes of rats were obvious in the model group. Compared with model group, the pathological changes of UL were relieved in the THSW group. Our data showed that the treatment of rats with THSW significantly reduced the expression of cytotoxic T lymphocyte associated antign 4 (CTLA4) and indoleamine 2, 3-dioxygenase 1 (INDO). The phosphorylation of JAK3 and STAT3 which are the main signal transduction molecule of cytokines and growth factorswere were also inhibited. Conclusions: Our results suggest that THSW is effective in the prevention and treatment of UL in rats, and THSW may exert its functions by inhibiting the activation of Tumor-related signal transduction pathway (JAK3/STAT3), immune escape, proliferation of tumor cell and improving apoptosis.