化合物MDPE的抗肿瘤活性

Antitumor activities of MDPE in vitro and in vivo

探讨化合物1-(3R,3aR)-8-甲基-3-(p-甲苯基)-3a,4-二氢硫色并[4,3-c]-1-乙酰基吡唑啉(MDPE)的体外和体内抗肿瘤生物活性.体外实验采用MTT法,研究MDPE对SGC7901,A549,Hela,HepG2,H22和S180细胞的生长抑制作用;体内实验研究MDPE对H22肝癌细胞皮下移植瘤和S180腹水瘤的抑制作用.结果显示:在体外实验中,MDPE对SGC7901,A549,Hela,HepG2,H22和S180细胞的生长抑制作用高于同浓度的顺铂,半致死质量浓度(IC50)分别为8.44,8.91,7.30,11.04,7.08和6.93μg/mL;在体内实验中,MDPE以每天给药1,5和10mg/kg的剂量灌胃给药,连续给药10d,对H22肝癌细胞小鼠皮下移植瘤的抑制率分别为45.33%,50.16%和51.73%,对S180腹水瘤小鼠的生命延长率分别为29.16%,56.66%和79.75%,此外,还考察MDPE对免疫系统和骨髓的影响.结果证实,MDPE是一种潜在的抗肿瘤药物,其作用机制等值得今后进一步深入研究.

In present study, the antitumor bioactivities of a novel synthesized chemical compound, 1 - （ （3R, 3aR）- 8 - methyl - 3 -（p-tolyl）- 3a, 4 - dihydrothiochromeno[4,3 - c] pyrazol - 2 （ 3H）- yl） ethanone （MDPE） were investigated in vitro and in vivo. Half maximal inhibitory mass concentrations （ICs0） of MDPE against six kinds of tumor cells （SGC7901, A549, Hela, HepG2, H22 and $180） were assessed by MTT method. And in vivo antitumor activity against H22 transplanted subcutaneously and $180 ascites tumor models were assessed by administering 1, 5 and 10 mg/kg/d of MDPE, intragastric administration, once a day for 10 consecutive days. In vitre MDPE showed IC50 values of 8.44, 8.91, 7. 30, 11.04, 7.08 and 6.93 μg/mL in SGC7901, A549, Hela, HepG2, H22 and S180 cells, respectively. In vitro, MDPE dose-dependently inhibited H22 transplanted tumor growth （inhibitory rates： 45.33%, 50.16% and 51.73%）, and enhanced mean survival time of S180 ascites tumor mice （rates of survival time： 29.16%,56.66~ and 79.75%）. Moreover, obvious impair of immune system and bone marrow suppression were observed. The results indicated that MDPE was a potential, prospective antitumor drug.