Guizhi Fuling Wan as a Novel Agent for Intravesical Treatment for Bladder Cancer in a Mouse Model.

Alternative intravesical agents are required to overcome the side effects currently associated with the treatment of bladder cancer. This study used an orthotopic bladder cancer mouse model to evaluate Guizhi Fuling Wan (GFW) as an intravesical agent. The effects of GFW were compared with those of mitomycin-C (Mito-C) and bacille Calmette-Guérin (BCG). We began by evaluating the response of the mouse bladder cancer cell line MB49 to GFW treatment, with regard to cell viability, cell cycle progression and apoptosis. MB49 cells were subsequently implanted into the urothelial walls of the bladder in female C57BL/6 mice. The success of the model was confirmed by the appearance of hematuria and tumor growth in the bladder. Intravesical chemotherapy was administered in accordance with a published protocol. In vitro data revealed that GFW arrested MB49 cell cycle in the G0/G1 phase, resulting in the suppression of cell proliferation and induced apoptosis. One possible mechanism underlying these effects is an increase in intracellular reactive oxygen species (ROS) levels leading to the activation of ataxia telangiectasia-mutated (ATM)/checkpoint kinase 2 (CHK2) and ATM/P53 pathways, thereby mediating cell cycle progression and apoptosis, respectively. This mouse model demonstrates the effectiveness of GFW in the tumor growth, with results comparable to those achieved by using BCG and Mito-C. Furthermore, GFW was shown to cause only mild hematuria. The low toxicity of the compound was confirmed by a complete lack of lesions on bladder tissue, even after 10 consecutive treatments using high concentrations of GFW. These results demonstrate the potential of GFW for the intravesical therapy of bladder cancer.

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.

Electroacupuncture induces differential effects between Yin and Yang: a study using cutaneous blood flow and temperature recordings of the hand's dorsum and palm.

The underlying theory of traditional Chinese Medicine (TCM) considers that Yin and Yang are in the opposition with each other and play different roles in physiological responses. Several studies have reported that electroacupuncture (EA) produces a greater effect than manual acupuncture (MA), and that the effect of EA is similar to transcutaneous electric nerve stimulation (TENS). Therefore, the purpose of the present study was to investigate the differences between Yin and Yang induced by acupuncture. A total of 20 healthy volunteers were studied. The cutaneous blood flow and temperature were recorded by a laser doppler perfusion and temperature monitoring system on the dorsum and palm of the right hand. Four sessions of sham acupuncture (SA), MA, 2 Hz EA, and 2 Hz TENS were bilaterally applied to Zusanli (ST36) and Shangjuxu (ST37) acupoints. Each of the subjects received four sessions in a random manner. The treatment interval was at least three days between sessions in order to prevent overlapping residual effects. Each of the four sessions was divided into pre-acupuncture period (BP), acupuncture period (AP), and post-acupuncture (PP) periods. Each treatment period was 15 min. Results indicated that the cutaneous blood flow recorded from the palm of the hand were greater than that recorded from the dorsum at the pre-acupuncture period; while the difference in the cutaneous temperature from the dorsum of the hand between AP and BP was greater in the 2 Hz EA session than in the SA and MA sessions. In conclusion, the results of the present study were consistent with the underlying theory of TCM that considers the fundamental differences between Yin and Yang.