本研究調查CHPS在BALB/c小鼠中對氧化偶氮甲烷(AOM)誘導和氧化偶氮甲烷(AOM)合併葡聚醣硫酸鈉(DSS)誘導模式中的結腸癌癌前病變和結腸癌的影響。
實驗一,由AOM誘導的小鼠結直腸前癌病變,隨機分為多個組別,並給予口服水和CHPS(100和300 mg/kg),為期6週的治療過程。結果表明,CHPS的治療顯著性的減少隱窩病灶(ACF)和異常隱窩(AC)的數目。 RT-PCR分析表明,口服CHPS能顯著降低aldose reductase,glutathione reductase,iNOS和β-catenin的mRNA表現量。初步結果表明,CHPS對AOM誘導小鼠結直腸癌癌前病變具有預防的效果。
實驗二,由AOM/DSS誘導的小鼠結直腸癌病變,小鼠結直腸癌誘導是腹腔注射AOM和在飲用水給予5% DSS。 AOM/DSS誘導小鼠,口服CHPS為期12週的治療過程。結果表明,CHPS的治療顯著性的減少息肉(Nodular)數目。 RT-PCR分析表明,口服CHPS能顯著降低Ctnnb1, IGF1R, iNOS 和 COX-2的mRNA表現量。 Western blot結果表明,在AOM / DSS誘導的小鼠中,口服CHPS能顯著降低β-catenin,PI3K,pAKT,pGSK3β的蛋白表現量。此結果表明,CHPS能改善AOM / DSS誘導的結直腸癌。
結論,本研究顯示,CHPS具有腸道的保護作用,有助於結直腸癌的防治。
This study investigated the effects of CHPS on BALB/c mice in azoxymethane (AOM)-induced and AOM/ dextran sodium sulfate (DSS)-induced preneoplastic lesions of colon and colorectal cancer in mice.
Experiment 1, The preneoplastic lesions of colon in mice with AOM treatments were separated into groups randomly and administrated with H2O and CHPS (100 and 300 mg/kg) via gastrogavage for 6 weeks. In the results, CHPS treatments caused a significant decrease in the number of aberrant crypt foci (ACF) and aberrant crypt (AC) on colon. RT-PCR analysis showed that AOM-treated mice expressed high levels of mRNA of aldose reductase, glutathione reductase, iNOS and β-catenin. CHPS treatment groups caused decreases in those gene expression. The initial results indicated that CHPS have preventive potential in AOM-induced preneoplastic lesions in the mice colon.
Experiment 2, colon cancer in mice were induced by intraperitoneal injection of AOM and animals received 5% DSS in the drinking water. AOM/DSS induced mice were orally treated with CHPS for entire period,12 weeks. In the results, CHPS treatments caused a significant decrease in the number of nodular on colon. RT-PCR analysis showed that AOM/DSS-treated mice expressed high levels of mRNA of Ctnnb1, IGF1R, iNOS and COX-2. Western blot analysis showed that AOM/DSS-treated mice expressed high levels of protein of β-catenin, PI3K, pAKT, and pGSK3β. CHPS treatment groups caused decreases in those genes and proteins expression. These results indicated that CHPS might exert inhibiting AOM/DSS-induced colon cancer
In conclusion, CHPS can act as an effective chemopreventive agents against preneoplastic lesions of colon and colorectal cancer.