Inhibitory Effects Of Combination Therapy Including Combretastatin A4Phosphate And Shiquandabu Decoction/Magnetic Fluid Hyperthermia In Hepatoma-xenograft Mice

Objective1.To investigate the effect of a Low-molecular-weight vascular-disrupting agent Combretastatin A4phosphate (CA4P) combination with Shiquandabu Decoction on growth of H22hepatoma xenograft mice and its mechanism.2.To investigate the effect of CA4P combination with Magnetic fluid Hyperthermia(MFH) on growth of H22hepatoma xenograft mice.Methods1.The liver cancer xenograft mode in mice was established H22cell.Seventy eight mice with liver cancer xenograft were randomly divided into six groups:I CA4P group; II Shiquandabu Decoction low-dose group; III Shiquandabu Decoction high-dose group; IV CA4P+Shiquandabu Decoction low-dose group; V CA4P+Shiquandabu Decoction high-dose group; VIcontrol group.The lenghth and width of xenograft were measured by vernier caliper at every three days during the therapy time.The volume of the xenograft was calculated,and xenograft grouth curves were ploted out.After28days,the tumor necrosis ratio was measured by MRI,the weight of primary subcutaneous xenograft and the inhibitory rate of weight of xenograft were examined after all mice sacrificed.Recipe blood from vein of eyeball centrifuging.The T cell subsets in peripheral blood were detected by FCM.The contents of IL-6and IFN-y of blood serum were detected by ELISA.The pathology form of xenograft were observed under microscop.2.The hepatoma-xenograft mice were constructed as moder,divided into four groups randomly:control group(NS),CA4P group(CA), Magnetic fluid Hyperthermia group(MFH) and CA4P+MFH group (CMFH). The lenghth and width of xenograft were measured by vernier caliper at every three days during the therapy time.The volume of the xenograft was calculated,and xenograft grouth curves were ploted out.The weight of primary subcutaneous xenograft and the inhibitory rate of weight of xenograft were examined at14days after the last hyperthermia after all mice sacrificed. The pathology form of xenograft were observed under microscop.Results1.(1)Comparing the tumor growth of all groups with that of control group,it hadn’t remarkable difference(P>0.05). The inhibitory rate of weight of subcutaneous xenograft in CA4P group,Shiquandabu Decoction low-dose group,Shiquandabu Decoction high-dose group,CA4P+low-dose group,CA4P+high-dose group,control group were respectively:4.43%、11.61%、20.46%、2.22%、6.62%.(2) In every treatment group the tumor necrosis ratio was increased, CA4P combination with Shiquandabu Decoction showed larger necrosis areas than CA4P group.(3) CA4P combination with Shiquandabu Decoction can increase CD3+、 CD4+、 CD8+T cell ratio in peripheral blood. CA4P can promote markedly production of IL-6and IFN-y, Shiquandabu Decoction can produce protective effect.2.In every treatment group xenograft growth was suppressed significantly.CA4P plus MFH group showed enhancement efficacy in anti-tumor growth(P<0.01).The inhibitory rate of weight of subcutaneous xenograft were respectively423%、63.3%、82.54%。 Pathological examination showed much larger necrosis areas in every treatment group.CA4P plus MFH showed the most obvious changes.Conclusions1.(1) CA4P combination with Shiquandabu Decoction can aggravate tissue necrosis in the xenograft,however,it can not inhibit the xenograft growth.(2) CA4P combination with Shiquandabu Decoction can promote the proliferation and activation of T cells, CA4P can significantly promote cytokines production, Shiquandabu Decoction exerts a protective action against this effect.2. CA4P combination with MFH can significantly inhibit the growth of H22hepatoma-xenograft in mice.