Compound SLXM-2, a derivative of cyclophosphamide （CTX）, has shown potent growth-inhibitory effect on tumor cells with low toxicity in previous studies. However, the mechanism of its anti-tumor effect, especially on...Compound SLXM-2, a derivative of cyclophosphamide （CTX）, has shown potent growth-inhibitory effect on tumor cells with low toxicity in previous studies. However, the mechanism of its anti-tumor effect, especially on DNA damage, remains largely unclear. This study investigated the effect of SLXM-2 on the survival time of mice transplanted with the ascitie fluid-type hepatocarcinoma 22 （H22）. We also evaluated the correlation between DNA damaging effect of SLXM-2 and its anti-tumor effect, and to probe the possible molecular mechanism for its effect on H22 cells. The results suggested that SLXM-2 significantly （P〈0.05） prolonged the survival time of mice bearing the ascitic fluid-type H22. Furthermore, SLXM-2 induced DNA damage in a dose-dependent manner in H22 cells. Further investigation revealed that SLXM-2 significantly （P〈0.05） up-regulated the expression levels of a series of DNA damage-related proteins, such as γH2AX （Ser139）, p-Chkl （Ser296）, p-Chk2 （Thr68）, p-p53 （Ser15）, p-p53 （Ser20） and p21, and down-regulated the expression of p-ATR （Ser428） and p-ATM （Ser1981）. In conclusion, SLXM-2 showed a remarkable anti-tumor activity on ascitic fluid-type H22 cells, and its molecular mechanism is related to its DNA damaging effect.展开更多
基金Eleventh Five Year Plan for National Science and Technology Major Project(Grant No.2009ZX0930010)
文摘Compound SLXM-2, a derivative of cyclophosphamide （CTX）, has shown potent growth-inhibitory effect on tumor cells with low toxicity in previous studies. However, the mechanism of its anti-tumor effect, especially on DNA damage, remains largely unclear. This study investigated the effect of SLXM-2 on the survival time of mice transplanted with the ascitie fluid-type hepatocarcinoma 22 （H22）. We also evaluated the correlation between DNA damaging effect of SLXM-2 and its anti-tumor effect, and to probe the possible molecular mechanism for its effect on H22 cells. The results suggested that SLXM-2 significantly （P〈0.05） prolonged the survival time of mice bearing the ascitic fluid-type H22. Furthermore, SLXM-2 induced DNA damage in a dose-dependent manner in H22 cells. Further investigation revealed that SLXM-2 significantly （P〈0.05） up-regulated the expression levels of a series of DNA damage-related proteins, such as γH2AX （Ser139）, p-Chkl （Ser296）, p-Chk2 （Thr68）, p-p53 （Ser15）, p-p53 （Ser20） and p21, and down-regulated the expression of p-ATR （Ser428） and p-ATM （Ser1981）. In conclusion, SLXM-2 showed a remarkable anti-tumor activity on ascitic fluid-type H22 cells, and its molecular mechanism is related to its DNA damaging effect.
