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The Chinese Journal of Dental Research

Year 2004
Volume 7 , Issue 4

Pages: 19 - 25

The Anticancer Effect of Two Forms of Hydroxycamptothecin on Oral Squamous Carcinoma Cell Line

Anxun Wang/Su Li/Xueqiang Ding/Hongzhang Huang

Objective: To study the anticancer effect and mechanism of two forms of hydroxycamptothecin (HCPT, ring-closed form: C-HCPT and ring-opened form: O-HCPT) in the treatment of oral squamous carcinoma cell line (Tca8113 cell line). Methods: Tca8113 cells and its xenografts in BALB/c nude mice were treated with two forms of HCPT. The cytotoxicity was measured by MTT assay and cell cycle was detected by flowcytometry. The growth state of Tca8113 cells xenografts were observed and the tumor doubling times and inhibition rate were calculated. The concentration of total HCPT in plasma and tumor tissues was quantitated by high-performance liquid chromatography (HPLC). Pharmocokinetic parameters were then estimated. Results: Both forms of HCPT produced similar cytotoxicity effects on Tca8113 cells in vitro. At low concentration of HCPT (<1 mol/L), cell cycle was arrested in S or G2+M phase; but as high concentration (100 mol/L apoptosis was obviously induced. Compared with control group, the xenografts of HCPT-treated group grew slowly and tumor doubling times prolonged. Tumor inhibition rate was 69.6% (3 mg/kg O-HCPT), 65.0% (3 mg/kg C-HCPT) and 74.1% (10 mg/kg O-HCPT), respectively. After administration of 10 mg/kg HCPT, the plasma AUC was 2.66 gh/mL (C-HCPT) and 0.42 gh/mL (O-HCPT). HCPT can be detected in tumor tissue. Conclusion: The result showed that both forms of HCPT had a strong cytotoxicity effect on oral squamous cell carcinoma cells in vitro and in vivo. HCPT can arrest cell cycle in S phase and G2+M phase and induce cell apoptosis.



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