一种新二萜类化合物的体外抗肿瘤研究

Antitumor effects of a new diterpene in vitro

目的研究一种新二萜类化合物凤厥内酯Ａ（Ｆ－Ａ）的抗肿瘤活性。方法采用体外培养的人癌细胞株——早幼粒细胞白血病ＨＬ－６０和红白细胞白血病Ｋ５６２作对象，观察Ｆ－Ａ对其抑瘤活性、诱导分化、细胞周期的影响。结果Ｆ－Ａ对ＨＬ－６０和Ｋ５６２细胞２４ｈ的半数抑制浓度ＩＣ５０分别为７．６ｍｇｇ－１和９．１ｍｇｇ－１，在４ｍｇＬ－１时即明显抑制ＨＬ－６０细胞的对数生长；对３Ｈ－ＴｄＲ参入作用在培养４８ｈ后有一定抑制作用；透视电镜显示肿瘤细胞有损伤表现；细胞周期分析显示Ｇ２＋Ｍ期细胞增多；ＮＢＴ还原反应试验阴性。结论Ｆ－Ａ明显抑制ＨＬ－６０和Ｋ５６２细胞生长，抗肿瘤活性强，对细胞周期的影响提示Ｍ期阻滞，研究初步提示Ｆ－Ａ不具细胞诱导分化作用。

AIM To determine the antitumor effects of a new diterpene (petrisolide A, FA) against human promyeloxytic leukemia HL60 and erythroleukemia K562 cell lines in vitro. METHODS Antitumor activity was measured using IC50, cell growth curve and 3HTdR uptake. Simultaneously, the cell cycle was analysed by flow cytometric(FCM) technique and the induced differentiation was tested by nitronblue tetrazolium(NBT) red uction. RESULTS IC50 of FA was 76 mg·L-1 to HL60 and 91 mg·L-1 to K562 respectively when incubation for 24 h. It obviously inhibited the growth curve of HL60 at 4 mg·L-1, the assays of 3HTdR incorporation into DNA showed a slight inhibition and the morphology was showed a cell damage under transmission electron microscopy (TEM) in the tumor cells of treated group. FCM analysis revealed that FA could arrest HL60 cells to G2+M phase and the S and G1 phase were not altered. In the tests of NBT reduction in the presence of FA at 4 mg·L-1 for 4 days, HL60 cells did not show NBT reductive ability. CONCLUSION FA remarkbly inhibited HL60 and K562 cell lines proliferation and showed a high antitumor activity. It was suggested that FA might inhibite mitoses of the cells and have not ability to induce differentiation.