Targeting GRP78 abrogates resistance to cetuximab and radiation.

<p>Oropharyngeal carcinoma cells transfected with siRNA to silence GRP78 or negative siRNA were treated with 50 μg/mL cetuximab for 12 h and then irradiated. (A) Colony formation experiments showed that cetuximab inhibited the colony formation of FaDu cells, which was further enhanced by silencing GRP78. In contrast, cetuximab alone did not affect the colony formation of Detroit562 cells, which was reversed by the silencing of GRP78. (B) Cetuximab weakened the radiation-mediated inhibition of FaDu cell proliferation, which was further enhanced by the silencing of GRP78. In addition, cetuximab had no significant effects on the radiation-mediated inhibition of Detroit562 cell proliferation, which was reversed by the silencing of GRP78. (C) Cetuximab increased the radiation-induced apoptosis of FaDu cells, which was further enhanced by the silencing of GRP78. The effect of cetuximab on the apoptosis of Detroit562 cells was not obvious, and this changed after GRP78 was silenced. Note: CTX = cetuximab, Neg = negative. *P < 0.05 Compared with Negative siRNA + IR; ΔP < 0.01 Compared with Negative siRNA + IR + CTX; ФP = 0.05 Compared with Negative siRNA + IR + CTX.