Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: Implications on chemoprevention

Figure 1 Histological examination of apoptosis and proliferation. Apoptosis was examined by apoptotic nuclei counting (A) and verified by TUNEL (B). A representative apoptotic nucleus is illustrated by the black arrow. Representative H&E stained sections showing apoptotic bodies (red arrow) in (C) MNNG-treated tumors, (D) celecoxib-treated tumors and (E) indomethacin-treated tumors. (F-H) Ki-67 immunostaining was used in the assessment of proliferation. Representative proliferating cells in (F) MNNG treated tumors, (G) celecoxib-treated tumors and (H) indomethacin-treated tumors indicated by positive immunoreactivity against Ki-67.

Figure 2 Effects of celecoxib/indomethacin treatment on gastric cell apoptosis and proliferation. A: Effects of celecoxib/indomethacin treatment on gastric cell apoptosis. The mean apoptotic index with standard error was shown. The apoptotic indexes were significantly higher in MNNG-induced tumor than in untreated control (P = 0.001). Moreover, the levels of apoptosis were significantly different among tumors (T), their adjacent non-tumor tissues (NT) and normal tissues from non-tumor rats (N) in all treatment groups (^aP<0.005, ANOVA). Treatment with celecoxib was associated with a higher apoptotic index in tumors (P<0.05, ANOVA) and their adjacent non-tumor tissues (P = 0.003, ANOVA). There appeared to be a dose-dependent increase in apoptotic index in celecoxib-treated tumors when compared to tumors treated with MNNG alone, but there was no significant increase in apoptotic index in indomethacin-treated tumors; B: The mean proliferation indexes with standard error. There were significant differences in the proliferation indexes among tumors (P≤0.001, ANOVA) and their adjacent normal gastric tissues (P = 0.01, ANOVA). Specifically, tumors in MNNG group had the highest proliferation index than other treatment groups (group B vs all other groups, P<0.003).

Figure 3 Effects of celecoxib or indomethacin on the apoptosis index to proliferation ratio (AI/PI) of gastric tumors. The mean AI/PI ratio with standard error was shown. There was a significant difference in the AI/PI ratio among different treatment groups (P = 0.026, ANOVA). The highest ratio was seen in gastric tumors treated with celecoxib at 10 mg/(kg·d) whereas the lowest ratio was seen in tumors from MNNG group. The AI/PI ratio appeared to inversely correlate with the tumor incidence reported in different treatment groups (Table 1).