Inhibitory Action Of Rosiglitazone Alone And In Combination With Paclitaxel In Ovarian Cancer Xenograft Model Of Nude Mice And Their Mechanism

Objective:we conducted this study to investigate the antitumor effect of rosiglitazone alone and in combination with paclitaxel in ovarian cancer xenograft model of nude mice.The expression of related protein was also determined in order to clarify their mechanism,which might provide basis for further research and management of ovarian cancer.Methods:SKOV3 cells were subcutaneously injected into flanks of nude mice for the preparation of ovarian cancer xenograft models.We randomized this models into A,B,C and D groups(6 mice/group).Rosiglitazone solution(4.0 mg/ml)was prepared with normal saline solustion and paclitaxel solution(6.0 mg/ml)with Oxygen ethyl castor oil and absolute ethyl alcohol(1:1).In group A,0.2ml normal saline solution was given to the mice by intragastric administration and 83ul medium of paclitaxel solution mentioned above by intraperitoneal injection;in group B,rosiglitazone solution(4.0 mg/ml)by intragastric administration and 83ul medium of paclitaxel solution mentioned above by intraperitoneal injection;in group C,0.2ml normal saline solution was given to the mice by intragastric administration and 83ul paclitaxel solution(6.0 mg/ml)by intraperitoneal injection;in group D,rosiglitazone solution(4.0 mg/ml)by intragastric administration and 83ul paclitaxel solution(6.0 mg/ml)by intraperitoneal injection.The frequency of intragastric administrations was every 2days;intraperitoneal injection every 4days.Tumor volumes were measured and recorded at the end of the experiment.Q value which could reflect the effect of the usage of rosiglitazone and paclitaxel on was then calculated according to Jin's formula.Furthermore,the expression of NF-KB,the apoptosis-associated protein,was determined through immunohistochemical staining in every group;the ultramicrostructure of ovarian cancer cells in ovarian cancer xenograft model in each group;the ultramicrostructure of tumor cells in all groups was observed by scanning electron micrograph.Results:the ovarian cancer xerograph model in nude mice could be prepared with the SKOV3 cells that grew well through proper techniques.The tumor inhibitory rate is up to 100%.The xerograph tumor volume were different in group A,B,C and D with the following order:group D>C>B>A in genaral.There were tumor inhibitory rates of 31.0%,45.7%,73.9%in group B,C and D respectively and thereby the Q value equaled to 1.8132 acording to Jin's formula that meaned the synergism of rosiglitazone and practexel in the inhibitory effect on xenograph cancer in nude mice.In addiction,down-regulation of NF-KB protein expression and apoptosis could be found obviously in the order of D>C>B>A,which might invovle in the mechanism of inhibitory effect of rosiglitazone and its synergism of this effect with practexel.On ovarian xerograph model in nude mice.Conclusion:1.rosiglitazone could inhibit the growth of SKOV3 xerograph tumor in nude mice.2.Rosiglitazone could enchance the inhibitory action of paclitaxel on SKOV3 xerograph tumor in nude mice in the form of synergism.3.the inhibitory effect of rosiglitazone and its synergism with paclitaxel on SKOV3 xerograph tumor in nude mice was associated with the promotion of apoptosis of tumor cells;the molecular mechanism was probably involved in the down-regulation of NF-KB expression.