Synergism of siRNA and Doxorubicin on Breast Cancer Cell Lines

Abstract

Breast cancer is the most common cancer among women of both developed and developing countries so far. Telomerase is expressed in many tumor tissues, including breast cancer. The tumor-specified expression of telomerase has made it a highly attractive cancer therapy target. Directly targeting telomerase may afford therapeutic benefit that extends beyond the effects of blocking telomere lengthening. One method of specified inhibition of telomerase is through RNA interference which has been shown since its discovery as a potent post-transcriptional gene silencing mechanism. Introduction of small interfering RNA (siRNA) can mediate the degradation of the mRNA, whose sequence is contained in the siRNA. The specific suppression of gene expression by RNA interference is evaluated as a potentially useful method for developing gene-silencing therapies for cancer.

RNA interference against human telomerase reverse transcriptase (hTERT), the protein component of telomerase, could successfully inhibit telomerase activity in several cancer cell lines. Doxorubicin is one of the most commonly used drugs to treat breast cancer. Monotherapy with doxorubicin has a good response rate; however, 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.