Topoisomerase II trapping agent teniposide induces apoptosis and G2/M or S phase arrest of oral squamous cell carcinoma

被引:21
作者
Li J. [1 ]
Chen W. [1 ]
Zhang P. [1 ]
Li N. [2 ]
机构
[1] Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University
[2] School of Medicine, Qingdao University
关键词
Oral Cancer; Oral Squamous Cell Carcinoma; Phase Arrest; Oral Squamous Cell Carcinoma Cell; Squamous Cell Carcinoma Cell;
D O I
10.1186/1477-7819-4-41
中图分类号
学科分类号
摘要
Background: Teniposide (VM-26) has been widely used in the treatment of small cell lung cancer, malignant lymphoma, breast cancer, etc. However, there are few reports on VM-26 against oral cancers. The present study was designed to identify the effect of VM-26 against oral squamous cell carcinoma in vitro, and to provide evidence for the feasibility and effectiveness of VM-26 for application to the patients with oral cancer. Methods: Human tongue squamous cell carcinoma cell line, Tca8113, was used. Cells were incubated with different concentrations of VM-26 for a variety of time span. Cisplatin (CDDP) was employed as a control reagent. MTT assay was used to assess the inhibitory rate of Tca8113 growth. Flow cytometer (FCM), transmission electronic microscope (TEM) and fluorescence staining were employed for determining the cell apoptotic rate. Cell cycle distribution of Tca8113 incubated with VM-26 was examined by flow cytometer assay. Statistic software (SAS 6.12, USA) was used for one-way ANOVA. Results: The IC50 of VM-26 against Tca8113 cells was 0.35 mg/l and that of CDDP was 1.1 mg/l. The morphological changes of Tca8113 cells were observed with fluorescence microscope and TEM. Apoptotic morphological feature could be found in the nucleus. Apoptotic rate of Tca8113 cells incubated with 5.0 mg/l of VM-26 for 72 hours was 81.67% and cells waere arrested at S phase. However, when exposed to 0.15 mg/l of VM-26 for 72 hours, G2/M phase increased from 12.75% to 98.71 %, while the apoptotic rate was 17.38%, which was lower than that exposed to 5.0 mg/l of VM-26. Conclusion: VM-26 could significantly induce apoptosis of oral squamous cell carcinoma and inhibit cell growth. There may be another pathway to induce apoptosis of oral squamous cell carcinoma cells except for G2/M phase arrest. © 2006 Li et al; licensee BioMed Central Ltd.
引用
收藏
相关论文
共 21 条
[1]  
Qiu W.L., Progress and achievements in diagnosis, treatment and research of oral tumors: 10-year review, Chinese Arch Otolaryngol Head Neck Surg, 3, pp. 57-61, (1996)
[2]  
Morse-Gaudio M., Risley M.S., Topoisomerase II expression and VM-26 induction of DNA breaks during spermatogenesis in Xenopus Laevis, J Cell Sci, 107, pp. 2887-2898, (1994)
[3]  
Andreassen P.R., Lacroix F.B., Margolis R.L., Chromosomes with two intact axial cores are induced by G2 checkpoint override: Evidence that DNA decatenation is not required to template the chromosome structure, J Cell Biol, 136, pp. 29-43, (1997)
[4]  
Mo Y.Y., Beck W.T., DNA damage signals induction of Fas ligand in tumor cells, Mol Pharmacol, 55, pp. 216-222, (1999)
[5]  
Heck M.M., Earnshaw W.C., Topoisomerase II, a specific marker for cell proliferation, J Cell Biol, 103, pp. 2569-2581, (1986)
[6]  
Liu L.F., DNA topoisomerase poisons as antitumor drugs, Annu Rev Biochem, 58, pp. 351-375, (1989)
[7]  
Bruden D.A., Osheroff N., Mechanism of action of eukaryotic topoisomerase II and drugs targeted to the enzyme, Biochim Biophys Acta, 1400, pp. 139-154, (1998)
[8]  
Bepler G., O'Briant K., In vitro chemosensitivity testing of human non-small cell lung cancer cell lines, Anticancer Res, 18, 5 A, pp. 3181-3185, (1998)
[9]  
Van der Gaast A., Splinter T.A., Teniposide (VM-26) in ovarian cancer: A review, Semin Oncol, 19, 2 SUPPL. 6, pp. 95-97, (1992)
[10]  
Nielsen D., Boas J., Engelholm S.A., Hansen O.P., Dombernowsky P., VM-26 in advanced breast cancer. A phase II trial in patients with no prior chemotherapy, Ann Oncol, 3, pp. 377-378, (1992)