After treatment with varying levels of Doxorubicin, about 50 percent more resistant cells in which Hsp27 had been forcefully activated died compared to normal drug-resistant cells. In addition, fluorescent staining of the cells showed that the expression of Hsp27 in these cells also caused them to absorb much more of the chemotherapy drug - a sign the drug was not being pumped away.

Additional experiments showed that these genetically altered cells died in the way they typically would in response to chemotherapy - by undergoing a programmed cell death process called apoptosis.

"We proved Doxorubicin does kill these cells in the way it is supposed to," Ilangovan said.

The findings represent a twist of sorts in molecular biology because heat-shock proteins typically are activated by stress. But in this case, the drug-resistant cells become reprogrammed over time - presumably, in response to the stress of being treated with drugs intended to kill them - and instead of being full of heat-shock protein activity, those stress-induced proteins are silenced.

"Because these proteins are involved, it looks at present like there could be a strong link between chronic stress and this drug-resistant mechanism evolving in the cells, but we need to carry out additional new studies to make any solid conclusion on chronic stress and drug resistance in cancer," Ilangovan said.

Translation of this technique in humans is years away, but would likely involve the delivery of the Hsp27 gene into drug-resistant cancer cells to induce activation of the Hsp27 protein, he said. The next step in this work involves refining the gene transfer process and demonstrating it in animal models.

Source: Ohio State University