Effects of Telomerase Inhibitors Combinated with Radiotherapy on Breast Cancer Xenograft in Mice
10.3321/j.issn:1000-467X.2001.03.005
- VernacularTitle:端粒酶抑制剂联合放射治疗对小鼠乳腺癌作用的实验研究
- Author:
Xiao-Feng RUAN
1
;
Yun-Feng ZHOU
Author Information
1. Hubei Medical University
- From:Chinese Journal of Cancer
2001;20(3):249-254
- CountryChina
- Language:Chinese
-
Abstract:
Objective：This study was designed to evaluate the treatment value of telomerase inhibitors for animal tumor in vivo and investigate radiosensitive effects of telomerase inhibitors. Methods：With orthogonal experiment design, the telomerase inhibitors(azidothymidine AZT 300 mg· kg -1· d -1, lamivudine 150 mg· kg-1· d -1)and radiotherapy (RT, 10 gray in a week, 2 gray/Fx, 5 Fx/wk) were used to treat breast cancers (MA782)xenograft in BALB/c mice for evaluating their influence on tumor size and telomerase expression. The tumor size was measured with a digital vernier scale. Telomerase activity was examined by a PCR-based telomeric repeat amplification protocol (TRAP) coupled with ELISA. Results：The tumor size of mice increased 2.7268 times in untreated and 2.5130 times in lamivudine-administrated, which indicated lamivudine having no obvious effect on tumor volume (P >0.05)； AZT, RT, and AZT combined with RT reduced tumor volume of 20.70％ , 47.43％ , and 85.19％ , respectively, and combined model(AZT＋ RT) was more effective than others used alone(P<0.05); The A value of tumor telomerase was untreated,0.817; AZT,0.453; lamivudine,0.760; RT,0.480; AZT 0.340 combined with RT； and AZT plus lamivudine plus RT,0.166 ; which suggested that AZT, RT and lamivudine could decrease the activity of tumor telomerase (P<0.05), and furthermore, AZT combined with RT have an additive effect (P< 0.05). Conclusion： Both AZT and radiotherapy are effective to treat murine breast cancer through decreasing telomerase activity and reducing tumor size. AZT can increase the radiation sensitivity for murine breast cancer MA782. Telomerase is a new target for anticancer treatment.
