Effcets Of HCPT On The Growth Of ACC SW-13Xenografts And The Transcription Of DKK-1and β-catenin

Objectives1. To observe the effects of HCPT on human ACC SW-13xenografts’growth.2. To investigate the effects and significance of HCPT on the transcriptionof DKK-1and β-catenin in ACC SW-13xenografts in nude mice.Methods1. Xenografts models are established by subcutaneous injection of SW-13cells into BALB/c nude mice. Tumor-bearing mice are treated HCPT withdifferent dose (treatment group A:3.0mg/kg·d, treatment group B:4.5mg/kg·d,treatment group C:6.0mg/kg·d) via ip qd×5d×2w (intraperitoneal injection onceper day,5times per week, use2weeks). HCPT is replaced by normal saline incontrol group.The volume of xenografts and the weight of nude mice aremeasured every other day.The changes of bodyweight (ΔBW), the optimal%T/C value and EFS T/C value are calculated to evaluate the antitumor effectsof HCPT.2. Xenografts models are established by subcutaneous injection of SW-13cells into BALB/c nude mice. Tumor-bearing mice are randomly divided into HCPT group (n=8) and control group (n=8). HCPT group are treated withHCPT4.5mg/kg·d via ip qd×5d×2w (intraperitoneal injection once per day,5times per week, use2weeks). HCPT is replaced by normal saline in controlgroup. Then the tumor-bearing mice are sacrificed, and the antitumor rate iscalculated. The transcription levels of DKK-1and β-catenin in SW-13xenografts are detected by quantitation real-time PCR (qRT-PCR).Results1. Tolerance: In treatment group A and B, the max lose of bodyweight are8%and18%respectively, and there is no drug related death. In treatment groupC, there are3tumor-bearing mice dead after d5, and the lose of bodyweight ofthe other5mice are above20%. Thus, stop to intervene and do not evaluate theantitumor effect in treatment group C.2. Antitumor effects: The optimal%T/C values of the treatment group Aand B both are below40%, suggesting HCPT have the treatment effects.Median EFS of treatment group A is longer than control group (8d vs5d,χ2=4.250, P=0.039), EFS T/C value is1.75, suggesting this treatment schemehas low antitumor effect. Median EFS of treatment group B is longer thancontrol group (17d vs5d, χ2=10.290, P=0.001), EFS T/C value is3.25,suggesting this treatment scheme has intermediate antitumor effect. There is nosignificant difference between the median EFS of treatment group A and B (8dvs17d, χ2=3.574, P=0.060).3. Tumor inhibition rate: The weight of HCPT group is less than controlgroup （1.54±0.55g vs0.64±0.29g, t=4.104, P=0.001）, tumor inhibition rate is58%.4. Results of realtime PCR: The relative expression level of DKK1mRNAin HCPT group is highter than control group (t=7.310, P <0.000). There is no significant difference in the relative expression level of β-catenin mRNA inHCPT group and control group (t=1.928, P=0.096).Conclusions1. HCPT can inhibit the growth of ACC SW-13xenografts in nude mice.2. HCPT can induce DKK-1mRNA transcriptional upregulation in SW-13xenografts, which might be one of the cause that HCPT inhibit tumor growth.3. HCPT has not significant effect on the transcription of β-catenin mRNAin SW-13xenografts, suggesting that HCPT induce DKK-1mRNAtranscriptional upregulation by manner of independent of β-catenin.