Targeting
heat shock protein 90 (Hsp90) provides a promising therapeutic approach to enhance the sensitivity of
tumor cells to ionizing radiation (IR). To explore the impact of scheduling
drug-IR administration, in the present study, we analyzed the response of lung
carcinoma A549 and
glioblastoma SNB19 cells to simultaneous
drug-IR treatment followed by a long-term
drug administration. Cellular response was evaluated at different time intervals after IR-alone,
drug-alone, or combined
drug-IR treatments by colony counts and expression profiles of Hsp90 and its clients, along with several apoptotic markers and cell cycle-related
proteins, as well as by IR-
drug-induced cell cycle arrest, DNA damage, and repair. A short 30-minute exposure to either Hsp90 inhibitor did not affect the radiosensitivity of both tumor cell lines. Increasing the duration of post-IR-
drug treatment progressively enhanced the sensitivity of SNB19 cells to IR. In contrast, the response of A549 cells to
drug-IR combination was largely determined by the cytotoxic effects of both drugs without radiosensitization. Combined
drug-IR treatment induced more severe DNA damage in both tumor cell lines than each treatment alone and also protracted the kinetics of DNA damage repair in SNB19 cells. In addition to large cell cycle disturbances,
drug-IR treatment also caused depletion of the antiapoptotic
proteins Akt and Raf-1 in both cell lines, along with a decrease of
survivin in A549 cells in case of
NVP-AUY922. The data show that simultaneous Hsp90 inhibition and irradiation may induce cell type-specific radiosensitization as well as cytotoxicity against
tumor cells.