Abstract | BACKGROUND:
Doxorubicin is an effective breast cancer drug but is hampered by a severe, dose-dependent toxicity. Concomitant administration of doxorubicin and another cancer drug may be able to sensitize tumor cells to the cytotoxicity of doxorubicin and lowers the therapeutic dosage. In this study, we examined the combined effect of low-dose doxorubicin and siRNA inhibition of telomerase on breast cancer cells. We found that when used individually, both treatments were rapid and potent apoptosis inducers; and when the two treatments were combined, we observed an enhanced and sustained apoptosis induction in breast cancer cells. METHODS: RESULTS: The hTERT siRNA effectively knocked down the mRNA and protein levels of hTERT, and reduced the telomerase activity to 30% of the untreated control. In vivo, the tumors induced by the hTERT siRNA-transfected cells were of reduced sizes, indicating that the hTERT siRNA also reduced the tumorigenic potential of the breast cancer cells. The siRNA treatment reduced cell viability by 50% in breast cancer cells within two days after transfection, while 0.5 microM doxorubicin treatment had a comparable effect but with a slower kinetics. The combination of hTERT siRNA and 0.5 microM doxorubicin killed twice as many cancer cells, showing a cumulative effect of the two treatments. CONCLUSION:
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Authors | Xuejun Dong, Anding Liu, Cindy Zer, Jianguo Feng, Zhuan Zhen, Mingfeng Yang, Li Zhong |
Journal | BMC cancer
(BMC Cancer)
Vol. 9
Pg. 133
(May 05 2009)
ISSN: 1471-2407 [Electronic] England |
PMID | 19416503
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- RNA, Small Interfering
- Doxorubicin
- Telomerase
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage)
- Apoptosis
(drug effects)
- Breast Neoplasms
(drug therapy, enzymology, genetics, therapy)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Combined Modality Therapy
- Doxorubicin
(administration & dosage)
- Female
- Genetic Therapy
- Humans
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- RNA, Small Interfering
(genetics, therapeutic use)
- Telomerase
(genetics, metabolism)
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