Telomerase Inhibition Plus Doxorubicin Boosts Apoptosis of Breast Cancer Cells

Last Updated: 2009-05-25 9:00:44 -0400 (Reuters Health)

By David Douglas

NEW YORK (Reuters Health) - In breast cancer cells, the cytotoxic effect of low-dose doxorubicin is enhanced by siRNA inhibition of telomerase, US and Chinese researchers report in a May 5th publication in BMC Cancer.

Telomerase is crucial in tumor proliferation, and as senior investigator Dr. Li Zhong of the City of Hope and Beckman Research Institute, Duarte, California, told Reuters Health, "Inhibition of the telomerase reverse transcriptase (hTERT) by the siRNA technique can be an effective treatment for breast cancer. When used in conjunction with doxorubicin, a common drug for breast cancer, it could potentiate the cytotoxic effect of the drug."

Dr. Zhong and colleagues note that because doxorubicin produces severe dose-dependent toxicity, any strategy to limit the dose could be helpful.

In vitro, transfection of hTERT siRNA into 2 breast cancer cell lines reduced telomerase activity to 30% of that seen in untreated control preparations, the researchers found.

Moreover, when siRNA-transfected breast cancer cells were injected into nude mice, the resulting tumors were of reduced size. In addition, within 2 days, siRNA treatment reduced the viability of breast cancer cells by 50%.

Doxorubicin had a similar but less rapid effect, and when the 2 treatments were combined, they killed twice as many cancer cells.

The investigators speculate that simultaneous delivery of doxorubicin and siRNA "may become feasible with a nanoparticle encapsulation system."

BMC Cancer 2009.


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