Xiaoyan Decoction’s Intervention on WISP2/CCN5 gene Knockdown Breast Cancer Transplanted Tumor Growth

Abstract Xiaoyan decoction, as a classical traditional Chinese medicine (TCM) formula, has been widely used for decades of years due to its safety and efficiency in tumor therapy. CCN5, also known as WISP-2(WNT-1 induced secreted protein 2) factor, plays an important role in inducing tumor cell apoptosis and inhibiting tumor proliferation. This study elucidated the mechanisms of inhibiting the WISP2/CCN5 gene knockdown nude mice tumor growth by Xiaoyan decoction. MCF-7 cells transfected by sh-WISP2/CCN5 were transplanted into nude mice and WISP2/CCN5 gene knockdown nude mice model was established. Xiaoyan decoction was orally administered to WISP2/CCN5 gene knockdown nude mice so as to intervene the growth of nude mice tumor model. As a result, the tumor volume of Xiaoyan decoction intervention group was significantly smaller,compared with WISP2/CCN5 gene knockdown group(P = 0.032). Besides, our study demonstrated that Xiaoyan Decoction was effective for raising the mRNA and protein levels of WISP2/CCN5 and p27Kip1, reducing the Skp2 mRNA and protein levels. Quantitative RT-PCR and western blotting were used to evaluated the mRNA and protein levels of WISP2/CCN5, Skp2 and p27Kip1. Increased mRNA and protein levels of WISP2/CCN5 and p27Kip1, decreased Skp2 mRNA and protein levels under the intervention by Xiaoyan decoction was found out in nude nice model. Overall, these results suggested that Xiaoyan decoction was an effective drug in inhibiting the growth of WISP2/CCN5 gene knockdown nude mice tumor, and WISP2/CCN5 might act as a potential anti-breast cancer target of Xiaoyan decoction.