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

• Published in: ACTA HISTOCHEMICA ET CYTOCHEMICA Vol. 32; no. 5; pp. 437 - 443
• Main Authors: Egawa, Masaaki, Chano, Tokuhiro, Matsumoto, Keiji, Okabe, Hidetoshi, Ishizawa, Michihito, Hukuda, Sinsuke
• Format: Journal Article
• Language: English
• Published: Sendai JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY 01.01.1999; Japan Science and Technology Agency
• Subjects: Apoptosis; Bromodeoxyuridine (BrdU); Cell kinetics; lododeoxyuridine (IUdR); Soft tissue sarcoma
• ISSN: 0044-5991; 1347-5800
• DOI: 10.1267/ahc.32.437

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). 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. 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.