Cell Kinetic of soft tissue sarcoma under the treatment of anti-cancer agents

为了阐明抗癌药物对软组织肉瘤的体内效应和动力学参数的变化，我们使用溴- (BrdU)和碘脱氧尿苷（IUdR）进行了双重标记。将一株恶性纤维组织细胞瘤细胞株移植到裸鼠体内，用顺铂、阿霉素、长春新碱3种抗癌药物治疗。测定以下参数：BrdU标记指数（LI）、s期持续时间（Ts）、细胞总周期时间（Tc）、Ki-67标记指数（KLI）、PCNA标记指数（PCNA-LI）、实际肿瘤体积倍增时间（Tv）。此外，采用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口端标记法（TUNEL）计算连续标本的凋亡细胞比率（凋亡指数，AI）。长春新碱抑制肿瘤生长效果最佳（Tv: -5.8 d）。阿霉素抑制肿瘤生长的效果（Tv: 12.7 d）优于顺铂（Tv: 9.1 d）。第1天TC值在各药物组间差异有统计学意义（方差分析，p<0.05），且与Tv值相关（Pearson分析，R < 0.7, p<0.05）。各给药组AI在第10天达到峰值，随后逐渐下降。抗肿瘤药物不仅能有效抑制肿瘤的坏死和凋亡，还能延长肿瘤的生长时间。Tc值可能对肉瘤患者的化疗计划有用。

To clarify in the vivo effects and the changes in kinetic parameters of soft tissue sarcoma caused by anticancer agents, we performed double-labeling using bromo- (BrdU) and iododeoxyuridine (IUdR). A malignant fibrous histiocytoma cell line was transplanted into nude mice, and treated with 3 anticancer agents : cisplatin, doxorubicin and vincristine. The following parameters were determined : BrdU labeling index (LI), duration of S-phase (Ts), total cell cycle time (Tc), Ki-67 labeling index (KLI), PCNA labeling index (PCNA-LI), and actual tumor volume doubling time (Tv). In addition, the apoptotic cell ration (apoptotic index ; AI) was calculated in the serial specimens using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL).Vincristine inhibited the tumor growth the most effectively (Tv : -5.8 days). Doxorubicin suppressed the tumor growth better (Tv 12.7 days) than cisplatin (Tv : 9.1 days). TC values showed significant differences among the drug groups (ANOVA analysis ; p<0.05), and also correlated with Tv (Pearson's analysis ; R>0.7, p<0.05) on Day 1. AI peaked on day 10 and decreased afterward in every drug group.Anticancer agents effectively suppress tumor growth not only by necrosis and apoptosis, but also by prolonged Tc. Tc values are possibly useful for planning chemotherapy for sarcoma patients.