Pdsw Combined With Whole Body Hyperthermia Treats Hepatocellular Carcinoma In Mice

Background. Recently, physiological deep-sea water (PDSW) from a depth of more than200m in depth is rich in trace metals, e.g., Se, Sr, and Zn which have been considered to be associated with prevention of carcinoma. Hyperthermia (HT) is a promising method for cancer treatment. We hypothesized that whole body hyperthermia would treat significantly hepatocellular carcinoma when combined with PDSW, and would improve heat tolerance and survival time in mice.Methods. In the first study, the effects of physiological deep-sea water on hyperthermal tolerance for Kunming (KM) mice in the45℃environment were exploredand. Deep-sea water (DSW) from the south Chinese sea was processed, and the metallic elements dissolved in the DSW were analysed. The animals were randomly divided into two groups with five animals:control group received tap water; the experimental group was treated with PDSW for15days. And then the animals fed in the45℃conditions. The survival time and histomorphometric analyses of the brain, lung, heart, liver and kidney were investigated.In the second study, the anti-cancer effects and enhanced resistance of PDSW in vitro and in vivo were investigated. In vitro, the cultured human hepatoma QGY-7703cells were randomly divided into tow groups:control group received saline;the experimental group received different concentrations of PDSW. Tow groups were heated respectively to6h of40℃or1h of43℃24,48,72hours after the administration of PDSW or saline, and QGY-7703cells proliferation capacity and toxicity were investigated by MTT assay. In vivo, the HCC-bearing Balb/c-nude mice were randomly divided into two groups with six animals:control group received tap water (TW); the experimental group was fed with PDSW of hardness3000for a further30days. And then tow groups of animal were heated to6h of40℃by the way of whole body hyperthermia every two day. Tumor volume and survival was evaluated. The histological appearance were measured by HE staining and transmission electron microscopy.Results. In the first study, the survival time in PDSW-fed group was significantly longer than in the control group (P<0.05).Moreover, histomorphometric analyses that PDSW could protect the brain, lung, heart, liver and kidney of KM mice from the45℃conditions. The results of western blot revealed that expression of HSP72of liver tissues for PDSW-fed group substantially increased, as compared to control mice (P<0.05).In the second study, the results of MTT assay showed that tumor inhibitory rate were time and concentration dependent in tow groups. Tumor inhibitory rate for PDSW group in different time were significantly higher than for the saline group (P<0.05), and the results revealed that PDSW could increased the anti-cancer sensitivity of HT in vitro. On the other hand,the inhibitory of hepatocyte for PDSW group in different time were significantly lower than for the saline group (P>0.05), and the results suggested that PDSW could protect the hepatocyte from HT in vitro.The change of tumor volume for the HCC-bearing Balb/c-nude mice fed with PDSW were not different compared with the TW (P>0.05), and the results showed the growth of tumor for the HCC-bearing Balb/c-nu mice weren’t enhanced by PDSW. But21days after HT, the tumor volume for the HCC-bearing Balb/c-nude mice fed with PDSW were smaller than with TW (P<0.05), and the results suggested PDSW could increased the anti-cancer effects of HT. Heating effect was advanced approximately by4days in the PDSW group compared with the TW group. The survival time of the PDSW group after HT were longer than of the TW group (P<0.05), and the results showed that PDSW could enhance heat tolerance and extend survival time for the HCC-bearing Balb/c-nude mice. A histological examination of the tumor revealed only a small necrotic area in the TW group as opposed to massive necrosis in the PDSW group. The percentage values of the necrotic area of the neo-graft tumor21days after HT were significantly larger for the PDSW group than for the TW group (P<0.01). The results of transmission electron microscopy suggested that necrosis was mainly event in the PDSW group, while apoptosis was mainly event in the TW group.Conclusions. Taken together, the results in the first study suggested that PDSW could improve hyperthermal tolerance of KM mice, which was considered the relation with HSP72expression resulted in PDSW.These results in the second study provided a possibility that continuous administration of PDSW can ameliorate tolerance in vitro or in vivo. PDSW significantly improved the survival time when combined with whole body hyperthermia, and could increased the anti-cancer effects of HT. This was supported by the histological findings and the results of MTT assay. These results might provide a novel and promising therapeutic option for HCC. The further mechanism would be explored in the future.