| Objective:To investigate the effect of Qi-Boosting Toxin-Resolving Formula (QBTRF) on the structure of cellular adhesion system in the implanted tumors with human nasopharyngeal carcinoma (NPC) cell line CNE2 among BALB/c nude mice and the regulatory effect on the signaling network of associated adhesive proteins to explore the underlying mechanisms responsible for intervening effect of herbal medicines with the effects of Qi-boosting toxin-resolving on metastasis of NPC cells from the viewpoint of cell adhesion intervene.Methods:Nude mice were used in this study to prepare implanted tumor models with human NPC cell line CNE2 by injecting method subcutaneously. Thirty two modeling mice were randomly divided into four groups, i.e.modeling group (MG), preventing group (PG) with QBTRF, treating group (TG) treated with QBTRF and positive control group (PCG).Then, they were treated with various treating procedures, with normal saline for the animals in MG,concentrated solution of QBTRF given 7 days before modeling for those in PG, concentrated solution of QBTRF given after modeling for those in TG, all given by forcedly oral perfusion, and methotrexate, injected intraperitoneally, for those in PCG respectively. Followed was observation on the dynamically growing status of implanted tumors during the experimental period among all groups, with growth curve drown by measuring the volumes of implanted tumors and body weight of animals every day for each group. By the end of experimental period, all the mice were put into death to dissect tumors for measuring the weight of implanted tumors for calculating the rate of implanted tumor growing-inhibiting, to take samples from the dissected tumors for histopathological observation on the cellular adhesive structure, by light microscopy and electron microscopy respectively. Meanwhile, immunohistochemistry was made to detect the expressive levels of Rac1,IQGAP1,E-Cadherin and P-catenin in tumor tissues from all groups of animals.Results:As measured on the volumes of implanted tumors after treatment with a comparative analysis with that of MG, there were statistically significant differences in the volumes of tumors among the nude mice of PG, TG and PCG (P<0.01-0.05),with the inhibitory rates of tumor growing being 58.35%,30.03% and 52.94% for them respectively.As shown under both of light microscope and electron microscope, tumor cells were in a status of proliferating productively in MG, with their nucleoli in bigger than that of the other groups as in PG, TG and PCG, for which the cellular adhesive structures were kept well,with smooth cellular perimeter and reduced digitations.Moreover, large areas of cellular necrosis could be found in the implanted tumor tissues in PG and TG, with lots of inflammatory cells infiltrating in these areas.As determined by SABC immunohistochemistry followed by image analysis on the cellular adhesion-relating proteins in sections of various groups,the expressive activities of Rac1 and IQGAP1 were much higher in the samples of MG than that of PG, TG and PCG, with significantly statistical differences among them (P<0.01).In the contrast, the expressive activities of E-Cadherin and (3-catenin were much higher in the tissue samples of PG, TG and PCG than that of MG, with significantly statistical differences among them as well (P<0.01).Conclusion:QBTRF holds significantly intervening effect on the changing characteristics of cellular adhesion related with the metastatic potentiality of implanted tumors prepared with NPC cell line CNE2 among nude mice, either given in a preventing way or in a treating way. The mechanisms underlying such an effect of QBTRF may be associated with the its inhibiting effect on the reduced tendency of cellular adhesive property in NPC cells.However, there may be somewhat different intervening mechanisms with the ways of herbal medicine given, such as the ways either in the goal of prevention or treatment.
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