[Inhibition of hydroxycamptothecin on laryngeal squamous carcinoma cell line].
OBJECTIVE
Hydroxycamptothecin(HCPT) has wide antitumor spectrum and high inhibition rate of tumor cell line and xenografts. Recently,no studies on the treatment of laryngeal squamous carcinoma with HCPT were reported. Hence,this study were designed to investigate the inhibition of O-HCPT [ring-opened form(O-HCPT)] and C-HCPT[ring-closed form(C-HCPT)] on laryngeal squamous carcinoma cell line(Hep-2 cell line)and its mechanism.


METHODS
The cytotoxicity of O-HCPT and C-HCPT on Hep-2 cells was measured by MTT assay and cell cycle was detected using flow cytometry (FCM). The growth state of Hep-2 cell xenografts treated with 10 mg/kg HCPT (O-HCPT or C-HCPT) was observed. The doubling time and the tumor inhibition rate were calculated.


RESULTS
The growth inhibition of O-HCPT and C-HCPT on Hep-2 cell depended on concentration. The IC(50) were 0.69 and 0.48 micromol/L, respectively. After treated with high concentration of HCPT, the cell cycle was arrested in S phase and then apoptosis were obviously induced. At the low concentration of HCPT, the cell cycle was slightly arrested in G(2)+M phase. Compared with control group, the xenografts of O-HCPT (10 mg/kg) treated group grew slowly and tumor doubling time prolonged. There was significant difference in the tumor volumes of two HCPT-treated group (P< 0.001) and the tumor inhibition rate was 77.0%. All mice in C-HCPT (10 mg/kg) treated group died of toxicity.


CONCLUSIONS
The result showed that O-HCPT and C-HCPT had obvious cytotoxicity to laryngeal squamous carcinoma cells which mechanism was HCPT arrest cell cycle in S phase and induce cell apoptosis. O-HCPT has slight toxicity effect and can be used as chemotherapeutic agent for laryngeal squamous carcinoma, but C-HCPT had strong toxicity.
Chai
Li-Ping
LP
Department of Otolaryngology,The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China. gzclp@sohu.com
Su
Zhen-Zhong
ZZ
Xian
Zhi-Xiong
ZX
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007822:Laryngeal Neoplasms / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000517:prevention & control; D016196:S Phase / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; C028098:10-hydroxycamptothecin; D002166:Camptothecin