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目的:研究10-羟基喜树碱(HCPT)的内酯环形式与抗癌活性之间的关系。方法:采用MTT和台盼蓝排染法测定两种内酯环形式的HCPT在体外对多种肿瘤细胞的作用,并在体内(0.5、1.0和2.0mg/kg,ip)评价它们对S_(180)肉瘤和HepS肝癌的抑瘤效果;应用HPLC方法观察了HCPT内酯环在肿瘤细胞内的转化情况。结果:两种形式的HCPT对同一种肿瘤细胞均显示类似的细胞毒性(P>0.05);但在体内实验中,闭环HCPT(C-HCPT)的抑瘤率明显高于(约两倍)开环HCPT(O-HCPT)。采用HPLC方法分析证明,两种类型的HCPT能在一定条件(如pH改变等)下相互转化。因此,O-HCPT体内、外作用的明显差异可归因于其在偏酸性环境(包括肿瘤细胞体外培养时)可较多地转化成C-HCPT,而在偏碱性环境(如正常体液pH约为7.40)中多呈开环形式。结论:闭环和开环HCPT羟基喜树碱均具有抗癌活性,但前者的活性较强;开环HCPT可在一定条件下转化成闭环形式。
AIM: To investigate the relationship between the lactone ring form of 10-hydroxycamptothecin (HCPT) and anti-cancer activity. METHODS: The effects of two lactone ring forms of HCPT on various tumor cells in vitro were assayed by MTT and trypan blue exclusion and evaluated in vitro (0.5, 1.0, and 2.0 mg / kg, ip) against S_ ( 180) sarcoma and HepS liver cancer; application of HPLC method observed HCPT lactone ring in the transformation of tumor cells. RESULTS: Both forms of HCPT showed similar cytotoxicity to the same tumor cells (P> 0.05). However, in vivo, the inhibition rate of HCPT (C-HCPT) was significantly higher than (about twice) Ring HCPT (O-HCPT). Analysis by HPLC showed that both types of HCPT can convert to each other under certain conditions (such as pH change). Thus, a significant difference in the in vitro and in vivo effects of O-HCPT can be attributed to the fact that it converts more into C-HCPT in acidic environments, including when the tumor cells are cultured in vitro, whereas in more alkaline environments such as normal body fluid pH About 7.40) mostly open-ring form. CONCLUSION: Both HCPT and HCPT have antitumor activity, but the activity of HCPT is stronger. The open-loop HCPT can be transformed into a closed-loop form under certain conditions.