Protective Effect of Curcumin Decreases Incidence of Gastric Cancer Induced by Helicobacter pylori and N‑methyl‑N‑nitrosourea in Rats

Aim: To study the effects of curcumin on Helicobacter pylori and N‑methyl‑N‑nitrosourea (MNU)‑induced gastric cancer in rats. Materials and Methods: Male Wistar rats were divided into three groups: control (CO), H. pylori inoculation and 30 ppm MNU in drinking water for 20 weeks (Hp + MNU), and H. pylori and MNU supplemented with 60 mg/kg curcumin for 30 weeks (Hp + MNU + Cur). The stomach was removed to examine nuclear factor kappa B (NF‑κB) p65, 8‑hydroxy‑2’‑deoxyguanosine (8‑OHdG), cyclin D1, and Ki‑67 in gastric epithelial cells by immunohistochemistry. The expression of apoptotic cells was measured by terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling reaction and gastric histopathology. Results: Two rats in Hp + MNU developed adenocarcinoma (ADC) of the glandular stomach (40% incidence, n = 5), while in Hp + MNU + Cur, no gastric ADC was found. Histopathology of gastric ADC showed the invasion of malignant cuboidal epithelial cells to submucosal layer. The percentages of NF‑κB p65, 8‑OHdG, cyclin D1, and Ki‑67 immunoreactive cells in Hp + MNU compared with CO were 12.20% ± 1.10% versus 1.86% ± 1.49%, 13.21% ± 0.90% versus 2.84% ± 1.29%, 66.96% ± 5.91% versus 6.06% ± 6.48%, and 42.29% ± 0.08% versus 14.95% ± 0.12%, P < 0.05, respectively. The expression of apoptotic cells significantly increased in Hp + MNU compared with CO (8.41% ± 0.01% vs. 0.53% ± 0.02%, P < 0.05). Curcumin supplementation reduced the gastric cancer incidence compared with Hp + MNU. Percentages of NF‑κB p65, 8‑OHdG, cyclin D1, and Ki‑67 immunoreactive cells in Hp + MNU + Cur compared with Hp + MNU were 4.76% ± 3.73% versus 12.20% ± 1.10%, 1.76% ± 0.94% versus 13.21% ± 0.90%, 24.71% ± 4.62% versus 66.96% ± 5.91%, and 24.99% ± 0.05% versus 42.29% ± 0.08, P < 0.05, respectively. The apoptosis expression was significantly improved (4.14% ± 0.16% vs. 8.41% ± 0.01%, P < 0.05). Conclusion: Curcumin can reduce gastric cancer incidence induced by H. pylori infection and MNU administration through the suppression of key proteins and apoptosis involved in carcinogenesis.