Abstract
Xuefu Zhuyu Decoction (XFZYD), a Traditional Chinese Medicine (TCM) decoction mainly for treating blood stasis syndrome, has been widely investigated and applied in clinic and in laboratory. XFZYD contains 11 herbs and has been identified to promoting blood circulation to remove blood stasis for cardiovascular disease. Meanwhile, blood stasis is directly related to malignant tumor according to TCM basic theory. However, the effects of XFZYD on tumor metastasis and the underlying mechanisms are still largely unknown. Here, we employed well-establishedDrosophilacell migration and tumor invasion models to explore whether XFZYD has the anticancer activity on tumor metastasisin vivo. Our work has demonstrated that XFZYD could suppress cell migration and tumor invasion at the moderate concentrations. In addition, XFZYD altered the expression of MMP1,β-integrin, and E-cadherin to impede cell migration. Moreover, XFZYD inhibited ocular tumor invasion presumably by reducing the activity of Notch signaling. Together, these evidences reveal a positive role of XFZYD in suppressing cell migration and tumor metastasis, providing the potential drug targets and key clues for cancer clinical treatment strategies.
Highlights
With the increased incidence, cancer has become a worldwide disease and represents one of serious health-care issues for human race [1, 2]
When Xuefu Zhuyu Decoction (XFZYD) high-performance liquid chromatography (HPLC) chromatogram was compared with the standard controls (Supplementary Figure 4a-c), we observed the distinguished peaks for paeoniflorin, ammonium glycyrrhizinate, and naringin in the chemical fingerprints of XFZYD (Figures 1(a)–1(c))
Considering cell migration is a central step for metastasis during tumorigenesis, we introduced a Drosophila ocular tumor invasion model, which is named eyeful [49], to further analyze the roles of XFZYD in metastasis
Summary
Cancer has become a worldwide disease and represents one of serious health-care issues for human race [1, 2]. More than 90% fatalities of human cancers are due to the ability of tumor metastasis at late stage, or form discontinuous secondary tumor foci at distant locations, instead of the localized primary tumor growth [3, 4]. After cancer enters the vascular and lymphatic vessels, these tumor cells survive and spread across the body through the circulatory system. They pierce through the vessel wall and settle at a secondary location to expand the metastatic focus [6,7,8]. Due to the adverse effects and high cost, synthetic chemotherapeutic anticancer drugs have not been as successful as expected in preventing and fighting against cancers in the clinic. The need to develop effective, safe, and affordable anticancer drugs from alternative and complementary herbal resources is becoming more and more urgent
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