The investigation of a traditional Chinese medicine, Guizhi Fuling Wan (GFW) as an intravesical therapeutic agent for urothelial carcinoma of the bladder.

BACKGROUND: The high risk of recurrence faced by patients with bladder cancer has necessitated the administration of supplemental intravesical chemotherapy; however, such treatments often result in severe side effects. As a result, novel intravesical agents with enhanced efficacy and minimal toxicity are urgently required for the treatment of bladder cancer. METHODS: Guizhi Fuling Wan (GFW) is a traditional Chinese medicine shown to inhibit the growth of hepatocellular carcinoma. This study evaluated the growth inhibition of GFW using normal human urothelial cells and bladder cancer cells; the efficacy of GFW treatment was further compared with mitomycin C, epirubicin, and cisplatin. We also examined the progression of cell cycle and apoptosis in bladder cancer cells in response to GFW treatment. CCK-8 was employed to analyze cell viability and flow cytometry was used to study the cell cycle and apoptosis. The mechanisms underlying GFW-induced cell cycle arrest were determined by Western blot analysis. RESULTS: Our data demonstrate the potent inhibitory effect of GFW in the proliferation of bladder cancer cell lines, BFTC 905 and TSGH 8301. GFW presented relatively high selectivity with regard to cancer cells and minimal toxicity to normal urothelial cells. Our results also demonstrate that GFW interferes with cell cycle progression through the activation of CHK2 and P21 and induces apoptosis in these bladder cancer cells. CONCLUSIONS: Our results provide experimental evidence to support GFW as a strong candidate for intravesicle chemotherapy against bladder cancer.

The role of TGF-beta 1 and cytokines in the modulation of liver fibrosis by Sho-saiko-to in rat's bile duct ligated model.

Liver fibrosis is an over-accumulation of extra-cellular matrix (ECM) and the hepatic stellate cell (Ito cell) play a central role in the pathogenesis of liver fibrosis. There are a lot of growth factors and cytokines involved in the activation of hepatic stellate cell, including of transforming growth factor (TGF-alpha, TGF-beta1), platelet-derived growth factor (PDGF), interleukin (IL-1alpha,beta, IL-6) and tumor necrosis factor (TNF-alpha). Sho-saiko-to (TJ-9; Xiao-Chai-Hu-Tang in Chinese) was the most popular herbal medicine for the treatment of chronic liver disease in Chinese and Japanese. Our aim of the current study was to examine whether TJ-9 regulated the growth factors and cytokines in the fibrogenesis of bile duct ligated model. Therefore, we assessed the TJ-9's potential in regulating TGF-beta1, PDGF mRNA expression, the amount of IL-1alpha, IL-1beta, IL-6, TNF-alpha and the fibrotic marker "PIII NP" in the serum. Then, using the immunohistochemical stain to observe the TGF-beta1 expression in the tissue. Our results showed that TJ-9 at a dose of 0.5 g/(kgday) significantly reduced the serum level of PIII NP, the mRNA expression of TGF-beta1 and PDGF. For the cytokines involved in the activation of Ito cell, TJ-9 at a dose of 0.5 g/(kgday) significantly suppressed the increasing tendency of IL-1beta and enhanced the production of TNF-alpha. Finally, we concluded that: (1) TJ-9 at a dose of 0.5g/(kgday) significantly reduced the serum fibrotic marker PIII NP in the bile duct ligated model, and its mechanism was partly by means of downregulating the mRNA of TGF-beta1 and PDGF. These results also confirmed by the immunohistochemical staining of TGF-beta1. (2) TJ-9 at a dose of 0.5 g/(kgday) suppressed the increasing tendency of IL-1beta and stimulated the production of TNF-alpha to inhibit Ito cell proliferation and collagen formation.

Sho-saiko-to prevents liver fibrosis induced by bile duct ligation in rats.

Hepatic fibrosis is an over-accumulation of extracellular matrix (ECM). It is a result of an imbalance between collagen synthesis and degradation. Matrix metalloproteinase (MMP) has degradative activity against collagen, but tissue inhibitors of metalloproteinase (TIMP) control the active forms of MMP by blocking the active site of MMP. In our study, we established the bile duct ligated model (BDL) in rats to evaluate anti-fibrotic potential of Chinese medicine sho-saiko-to (TJ-9). We assessed the drug's potential in inhibiting collagen accumulation, suppressing procollagen alpha1 types (I) and (III), and TIMP-1 mRNA expression. After administration of TJ-9, hyperbilirubinemia reduced approximately four-fold when compared with BDL-untreated group. TJ-9 also significantly reduced the collagen content and fibrogenic score, as well as downregulated elevated procollagen alpha1 types (I) and (III) and TIMP-1 mRNA level. Finally, we concluded that (1) TJ-9 significantly reduced cholestasis in rats with BDL, (2) TJ-9 markedly reduced the collagen content by 50%, and (3) TJ-9 exerted its antifibrogenic effect by downregulation of the mRNA expression of procollagen alpha1 types (I) and (III), and TIMP-1 in liver tissue.