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

为了阐明在体内的影响和抗癌药物引起的软组织肉瘤的动力学参数的变化，我们进行了双标记使用溴-（BrdU）和碘脱氧尿苷（IUdR）。将恶性纤维组织细胞瘤细胞株移植于裸鼠体内，并分别用顺铂、阿霉素和长春新碱进行治疗。测定BrdU标记指数（LI）、S期持续时间（Ts）、总细胞周期时间（Tc）、Ki-67标记指数（KLI）、PCNA标记指数（PCNA-LI）和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末端标记法（TUNEL）检测肿瘤细胞凋亡指数（AI），结果表明，阿曲斯汀对肿瘤生长的抑制作用最强（Tv：-5.8天）。多柔比星抑制肿瘤生长（Tv 12.7天）优于顺铂（Tv：9.1天）。TC值在药物组之间显示出显著差异（ANOVA分析; p<0.05），并且还与第1天的Tv相关（Pearson分析; R>0.7，p<0.05）。各药物组AI均在第10天达到峰值，随后下降，抗癌药物不仅通过坏死和凋亡，而且通过延长Tc来有效抑制肿瘤生长。Tc值可能有助于肉瘤患者的化疗计划。

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.