Resistance to paclitaxel increases the sensitivity to other microenvironmental stresses in prostate cancer cells

The microenvironment is central to many aspects of cancer pathobiology and has been proposed to play a role in the development of cancer cell resistance to therapy. To examine the response to microenvironmental conditions, two paclitaxel resistant prostate cancer (PCa) cell lines (stable and reversible) and one reversible heat resistant cell line were studied. In comparison to their parental cell lines, both paclitaxel resistant cell lines (stable and reversible) were more sensitive to microenvironmental heat, potentially yielding a synergistic therapeutic opportunity. In the two phenotypic cells repopulated after acute heat or paclitaxel treatments, there was an inverse correlation between paclitaxel and heat resistance: resistance to paclitaxel imparted sensitivity to heat; resistance to heat imparted sensitivity to paclitaxel. These studies indicate that as cancer cells evolve resistance to single microenvironmental stress they may be more sensitive to others, perhaps allowing us to design new approaches for PCa therapy.