Kinetic Analysis of Malignant Fibrous Histiocytoma Cells Treated with Anticancer Agents In Vivo.

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  • Egawa Masaaki
    Department of Orthopaedic Surgery, Shiga University of Medical Science
  • Chano Tokuhiro
    Department of Orthopaedic Surgery, Shiga University of Medical Science
  • Matsumoto Keiji
    Department of Orthopaedic Surgery, Shiga University of Medical Science
  • Okabe Hidetoshi
    Department of Clinical Laboratory Medicine, Shiga University of Medical Science
  • Ishizawa Michihito
    Department of Orthopaedic Surgery, Shiga University of Medical Science
  • Hukuda Sinsuke
    Department of Orthopaedic Surgery, Shiga University of Medical Science

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Abstract

To clarify the in 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 ratio (apoptotic index; Al) was calculated in the serial specimens using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL).<br>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. Al peaked on Day 10 and decreased afterward in every drug group.<br>Anticancer agents effectively suppress tumor growth not only by necrosis and apoptosis, but also by prolonging Tc. Tc values are possibly useful for planning chemotherapy for sarcoma patients.

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