Effects of treatment with metformin, gefitinib and a combination of metformin and gefitinib, on the growth of PC9 xenograft tumors in SCID mice. After growing tumors for 16 days, the animals were randomly divided into 4 groups. In group 1 (fine broken line), saline (p.o.) was administered daily for 14 days (until day 30) and PBS (i.p.) was then administered daily until terminating the observation (day 66). In group 2 (fine, solid line), gefitinib (p.o., 150 mg/kg/day) suspended in saline was administered daily for 14 days and PBS (i.p.) was then administered daily until day 66. In group 3 (thick, broken line), saline (p.o.) was administered daily for 14 days and metformin (i.p., 250 mg/kg/day) dissolved in PBS was then administered daily until day 66. In group 4 (thick, solid line), both gefitinib and metformin were administered. The regrowth of the tumors after withdrawing gefitinib was significant, with each given p-value in the figure, suppressed by metformin (compare groups 3 and 4), whereas metformin exerted no effects on tumor growth (compare groups 1 and 2) and tumor shrinkage by gefitinib (compare groups 3 and 4). Each point represents the mean and the bars represent the SE (n=7).