Researchers have discovered 87 genes that seem to affect the sensitivity of human cancer cells to Paclitaxel. When the researchers blocked the action of some of the 87 genes inside isolated lung-cancer cells, they found that those cells were up to 10,000 times more sensitive to Paclitaxel.
UT Southwestern Medical Center scientists used a library of 84,508 different siRNA molecules to screen all 20,000-plus human genes for biological activity. A robot was used to place four siRNAs, which blocked the function of a single gene, into each well of a 96-well plate. Non-small-cell-lung cancer cells were placed in each well and Paclitaxel was added to each well for two days. By examining the survival of the cells in each well, the researchers determined which genes were involved in affecting the cells’ sensitivity to the drug.
The researchers then re-tested the six genes that showed the most dramatic effect with Paclitaxel and tried the same test using chemotherapy drugs Vinorelbine and Gemcitabine, but the results were not as dramatic as those seen for Paclitaxel.
"Our studies using additional drugs indicate that the genes we uncovered are highly specific for Paxlitaxel," points out Angelique Whitehurst, postdoctoral researcher in cell biology and lead author of the study.
The study is available online and appeares in the April 12 edition of Nature.