Figure 2.
Efficacy of chemotherapy is inversely dependent on the percentage of quiescent/dormant cancer cells. (A) Representative image of cross section of nascent tumor (3 d after cancer cell inoculation), intermediate tumor (7 d after cancer cell inoculation), and established tumor (14 d after cancer cell inoculation). Experimental setup; FUCCI-expressing MKN45 cells (5×106 cells/mouse) were injected subcutaneously into the left flanks of mice. Mice were intraperitoneally injected with cisplatinum (CDDP) (4 mg/kg) 3 d after inoculation, 7 d after inoculation, or 14 d after inoculation for 3 cycles every 3 d. (B) Representative images of CDDP-treated FUCCI-expressing MKN45 subcutaneous tumors. Nascent tumor (treatment started 3 d after inoculation) (upper). Intermediate tumor (treatment started 7 d after inoculation) (middle). Established tumor (treatment started 14 d after inoculation) (lower). (C) The relationship between antitumor efficacy of CDDP and the percentage of quiescent cancer cells. (D) Bar graphs show the relationship between rate of recurrent tumor growth and the cell-cycle status of tumors. The cells in G0/ G1, S, or G2/M phases appear red, yellow, or green, respectively. Data are shown as means ± SD (n = 5). Scale bars, 500 μm.