Bortezomib sensitizes human head and neck carcinoma cells SQ20B to radiation.
The proteasome inhibitor bortezomib was tested in a cell screen as a single agent with good efficacy in multiple hematologic and solid cancer cell lines. Phase II/III studies have supported the use of bortezomib in hematologic malignancies. In solid tumors, however, the results have been poor. There is data that bortezomib can induce PTEN expression resulting in down-regulation of PI3K-Akt signaling. We and others have shown that down-regulation of Akt results in radiation sensitization. We therefore evaluated the use of bortezomib in the head and neck cancer cell line SQ20B as a radiation sensitizer. SQ20B have a constitutively active mutation in EGFR resulting in a robust Akt response. We found that 10 nM of bortezomib decreased Akt signaling to almost undetectable. This same concentration decreased the surviving fraction after 2 Gy (SF2) from 0.77 to 0.45. Given that radiation is usually given at 2 Gy increments daily for 30 or more treatments, the exponential difference in log kill could be as high as 7 logs. The dose of bortezomib is also 2 logs less as a sensitizer than that required for single agent efficacy. Further studies should be done to explore this model in vivo.
Weber
Charles N
CN
Department of Radiation Oncology, University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104, USA.
Cerniglia
George J
GJ
Maity
Amit
A
Gupta
Anjali K
AK
D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D011719:Pyrazines / Q000627:therapeutic use*; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D011838:Radiation-Sensitizing Agents; D000069286:Bortezomib