O^(6)-苄基鸟嘌呤增强1,3-二(2-氯乙基)-亚硝基脲对人肝癌细胞及其移植瘤的抗肿瘤作用(英文)

Potentiation of 1,3-bis(2-chloroethyl)nitrosourea anticancer activity on hepatocarcinoma cell line and its xenograft by O^(6)-benzylguanine

应用噻唑蓝 (MTT)法检测 O6-苄基鸟嘌呤(O6- BG)与 1 ,3-二 (2 -氯乙基 ) -亚硝基脲 (BCNU)合用的细胞毒作用及透射电镜检测凋亡细胞的方法研究了 O6- BG对 O6-烷基鸟嘌呤 - DNA烷基转移酶(O6- AGT )阳性的人肝癌细胞 SMMC- 772 1对BCNU细胞毒作用敏感性的影响及其与 BCNU合用治疗移植瘤的协同效果 .结果显示 :1 .5- 6.0 mg· L-1的 O6- BG预先作用 2 h后 ,SMMC- 772 1细胞对 BCNU的敏感性明显增加 ;0 .75- 6.0 mg· L-1的 O6- BG可完全快速地抑制肿瘤细胞的 AGT活性并持续 1 2 h;ip 90 mg· kg-1的 O6- BG预处理 2 h后给予 2 5mg·kg-1的 BCNU治疗 ,可使动物 sc接种的人肝癌移植瘤生长延迟 38.6d,诱导肿瘤细胞凋亡 ,并且可明显抑制肿瘤组织的转移酶活性 .说明 O6- BG与 BCNU合用于

To evaluate the effect of O 6 benzylguanine(O 6 BG) on the sensitivity of O 6 alkylguanine DNA alkyltransferase(O 6 AGT)positive cell lines, human hepatocarcinoma cells SMMC 7721, to cytotoxicity of 1,3 bis(2 chloroethyl) nitrosourea (BCNU). To evaluate synergetic efficacy of O 6 BG and BCNU in treatment of human tumor xenograft. Cytotoxicity of O 6 BG and BCNU to tumor cell lines was evaluated by using 3 (4,5 dime thylthiazol 2 yl) 2,5 diphenyl tetrazolium bromide (MTT) assay. Alkyltransferase activity was measured as removal of O 6 [ 3H]methylguanine from a [ 3H]methylated DNA substrate (740 PBq·mol -1 ). We determined apoptosis by transmission electronic microscopy(TEM). The results showed that the sensitivity of SMMC 7721 cells to BCNU was increased by pretreatment for 2 h with 1.5-6.0 mg·L -1 O 6 BG. 0.75-6.0 mg·L -1 O 6 BG completely and rapidly suppressed O 6 AGT activity of cells persisted up to 12 h. When given ip 2 h before BCNU(25 mg·kg -1 ) to animals bearing tumors, O 6 BG(90 mg·kg -1 )produced a tumor growth delay of 38.6 d in human hepatocarcinoma xenograft and induced evident apoptosis. Further more, O 6 BG significantly inhibited O 6 AGT activity of tumor tissue. It suggests that combination of O 6 BG with BCNU have a significant therapeutic effect in the treatment of O 6 AGT positive tumor.