Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated of Jiangsu University, Changzhou 213017, China.
Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.
Nutrients. 2022 Dec 11;14(24):5281. doi: 10.3390/nu14245281.
Gastric cancer is a common malignant tumor worldwide. -methyl--nitro--nitroguanidine (MNNG) is one of the most important inducing factors of gastric cancer. Autophagy can affect the occurrence and development of gastric cancer, but the mechanism is not clear. Chemoprevention has been shown to be a rational and very promising approach to the prevention of gastric cancer. Hesperidin is a citrus flavone, an abundant polyphenol in citrus fruits and traditional Chinese medicine. It has an excellent phytochemistry that plays an intervention role in gastric cancer. However, it is unclear whether long-term exposure to MNNG will affect the occurrence of gastric cancer by regulating autophagy and whether hesperidin can play an intervention role in this process. In the present study, we demonstrated that long-term MNNG exposure inhibits autophagy in stomach tissues of rats, promotes the epithelial-mesenchymal transition (EMT) process and cell proliferation and suppresses the activity of the PI3K/AKT pathway. We further found that after rapamycin-activated autophagy, long-term MNNG exposure promoted cell proliferation and EMT were inhibited. In addition, hesperidin promotes autophagy and the activity of the PI3K/AKT pathway, as well as the suppression of proliferation and EMT in the stomach tissues of rats. Our findings indicate that hesperidin reverses MNNG-induced gastric cancer by activating autophagy and the PI3K/AKT pathway, which may provide a new basis for the early prevention and treatment of MNNG-induced gastric cancer.
胃癌是一种常见的全球恶性肿瘤。-甲基--硝基--硝基胍（MNNG）是胃癌最重要的诱导因素之一。自噬可以影响胃癌的发生和发展，但机制尚不清楚。化学预防已被证明是预防胃癌的一种合理且非常有前途的方法。橙皮苷是一种柑橘类黄酮，是柑橘类水果和中药中丰富的多酚类化合物。它具有出色的植物化学性质，在胃癌中发挥干预作用。然而，尚不清楚长期 MNNG 暴露是否会通过调节自噬来影响胃癌的发生，以及橙皮苷是否可以在这个过程中发挥干预作用。在本研究中，我们证明了长期 MNNG 暴露抑制了大鼠胃组织中的自噬，促进了上皮-间充质转化（EMT）过程和细胞增殖，并抑制了 PI3K/AKT 通路的活性。我们进一步发现，在雷帕霉素激活自噬后，长期 MNNG 暴露促进了细胞增殖，抑制了 EMT。此外，橙皮苷促进了自噬和 PI3K/AKT 通路的活性，以及大鼠胃组织中增殖和 EMT 的抑制。我们的研究结果表明，橙皮苷通过激活自噬和 PI3K/AKT 通路逆转了 MNNG 诱导的胃癌，这可能为 MNNG 诱导的胃癌的早期预防和治疗提供新的依据。
