Figure 6. Enhancement of the therapeutic effect of Erlo on xenograft lung cancer by Met.

Human lung cancer cell line A549 (5 × 10⁶) in 200 μl PBS were subcutaneously injected into the left flank of nude mice. One week after implantation when tumors reached a volume of 4-6 mm³, mice were intraperitoneally injected with 250 mg/kg Met or 50 mg/kg Erlo or in combination, every 5 days for 5 cycles. The Erlo solvent Captisol (6%) was injected in control tumor bearing mice. At the indicated days post tumor cell implantation, tumor size was measured and at 30 days, mice were euthanized and tumors were harvested for histological examination. (A) Photographs of xenograft tumors at day 30 after A549 cell implantation. Veh: Captisol; Met: metformin; Erlo: erlotinib. (B) Growth kinetics of xenograft tumors in nude mice with or without treatment with Met or Erlo or in combination. ^* denotes significantly (P < 0.05) reduced size of tumors in mice treated with Met, Erlo, or in combination. ^** p < 0.01; ^*** p < 0.001. (C) Ki67 staining for xenograft tumors at day 30 after A549 cell implantation, Red: Ki67, Blue: DAPI; Scale bar: 50 μm. (D) The Ki67⁺ cells from xenograft tumors at day 30 after A549 cell implantation were quantified. N = 15-21, 3-5 mice per group. ^* p < 0.05; ^** p < 0.01; ^*** p < 0.001.