Fig. 5.

KRA-533 potently suppresses tumor growth in KRAS mutant lung cancer xenografts. (a) Nu/Nu nude mice with A549 xenografts bearing mutant KRAS were treated with increasing doses of KRA-533 (0, 7.5, 15, and 30 mg/kg/d) for 28 days (n = 6). Tumor volume was measured once every 2 days (left panel). Tumor volumes of 6 individual mice in each group were compared on day 28 (right panel). After 28 days, the mice were sacrificed, and the tumors were removed and analyzed. Data represent mean ± SD, n = 6 per group. *P < 0.05, **P < 0.01, by 2-tailed t test. (b) Active caspase-3, LC3-II and p-ERK were analyzed by IHC staining in tumor tissues at the end of experiments and quantified. Data represent mean ± SD, n = 6 per group. *P < 0.05, **P < 0.01, by 2-tailed t test. (b) KRAS-GTP (active form of KRAS) was pulled down by Raf-1-RBD from tumor tissue lysates, followed by Western blot using KRAS antibody. Expression levels of active caspase-3, cleaved PARP, Beclin-1 and LC3-II in tumor tissues were analyzed by Western blot