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化合物SLXM-2是一种环磷酰胺衍生物,前期研究已经证实其具有良好的肿瘤抑制作用,并具有较低的毒副作用。但是其作用机制尤其是对细胞DNA的损伤作用仍不清楚。本研究旨在评价SLXM-2对肝癌H22腹水小鼠的生命延长作用与DNA损伤的关系,并探讨可能的分子机制。实验结果证实,SLXM-2能够显著提高肝癌H22腹水小鼠的生命延长率(P<0.05)。进一步实验表明,SLXM-2能够造成肝癌H22细胞DNA损伤,显著上调γH2AX(Ser139),p-Chk1(Ser296),p-Chk2(Thr68),p-p53(Ser15),p-p53(Ser20)和p21的蛋白表达,并显著下调p-ATR(Ser428)和p-ATM(Ser1981)的表达(P<0.05)。总之,SLXM-2对肝癌H22细胞具有显著的抑制作用,分子机制与其能够造成肿瘤细胞DNA损伤有关。
Compound SLXM-2 is a cyclophosphamide derivative. Previous studies have shown that it has good tumor inhibition and has low toxicity. However, its mechanism of action, especially the role of DNA damage cells is still not clear. The purpose of this study was to evaluate the relationship between SLXM-2 life-prolonging effect and DNA damage in H22 ascites mice and to explore possible molecular mechanisms. The experimental results confirmed that SLXM-2 can significantly improve the life extension rate of H22 ascites mice (P <0.05). Further experiments showed that SLXM-2 could induce DNA damage in H22 cells and up-regulate the expression ofγH2AX (Ser139), p-Chk1 (Ser296), p-Chk2 (Thr68), p-p53 p21 protein expression, and significantly downregulated the expression of p-ATR (Ser428) and p-ATM (Ser1981) (P <0.05). In conclusion, SLXM-2 has a significant inhibitory effect on H22 cells, and its molecular mechanism is related to its ability to cause DNA damage in tumor cells.