CHEMOSENSITIZATION BY BI-FUNCTIONAL SMALL HAIRPIN RNA (bi-shRNA)

摘要

Compositions and methods of augmenting the anti-tumor activities of docetaxel and other taxanes by combination with a bi-functional small hairpin RNA (bi-shRNA) is described herein. The instant invention describes the interactive outcome of STMN1 knockdown with docetaxel. In vitro docetaxel (DOC) dose response assessments with or without co-treatment with bi-shRNASTMN1 in CCL-247 and SK-MEL-28 melanoma cells indicated that STMN1 knockdown significantly reduced DOC concentration needed to inhibit cancer cell growth by 50% (IC50) of CCL-247 cells from 1.8±0.2 to 0.6±0.4 nm (n=3, p<0.05), and SK-MEL-28 cells from 1.7±0.2 nm to 0.1±0.0 (n=3, p<0.05). The 3- to >10-fold reduction in DOC IC50 suggest that bi-shRNASTMN1 can markedly enhance the effectiveness of docetaxel for human cancer cells.