RESUMEN
ObjectiveTo investigate the effect of Qi-invigorating and blood-activating therapy on the miR216b/Beclin1 pathway in mice with atrophic precancerous lesions of gastric cancer （PLGC） and analyze its mechanism in autophagy of PLGC. MethodSeventy-five healthy male SPF KM mice were randomly divided into a blank group and a model group. Mice in the model group were given 1-methyl-3-nitroso-1-nitrosoguanidine （MNNG） solution （150 mg·L-1） for free drinking and gavage and ranitidine solution （0.03 g·kg-1） daily for 12 weeks. According to the random control table， mice were divided into a model group， a Qi-invigorating group （3.5 g·kg-1 of Astragali Radix）， a blood-activating group （0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder）， a Qi-invigorating and blood-activating group （3.5 g·kg-1 of Astragali Radix + 0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder）， and a folic acid group （2 mg·kg-1）. The corresponding drugs were given to mice in each group for 8 weeks and then the tissues were collected. Hematoxylin-eosin （HE） staining was carried out to observe the changes in gastric mucosa. Western blot was used to detect the protein expression of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， and Beclin1. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Beclin1 and miR-216b. ResultPathological observation showed that as compared with the blank group， the intrinsic glands of gastric mucosa decreased with atrophy and intestinal metaplasia in the model group， which were improved in all treatment groups， and the improvement of the Qi-invigorating and blood-activating group was the most obvious. As compared with the blank group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of the model group was significantly decreased （P<0.05）. As compared with the model group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of each treatment group was increased （P<0.05， P<0.01）. The increase was most obvious in the Qi-invigorating and blood-activating group. As compared with the blank group， the mRNA expression of Beclin1 in the model group was decreased （P<0.05）， and that of miR216b was increased （P<0.05）. As compared with the model group， the mRNA expression of Beclin1 was increased and that of miR216b was decreased in each treatment group （P<0.05）， and the changes were the most obvious in the Qi-invigorating and blood-activating group. ConclusionThe mechanism of the Qi-invigorating and blood-activating therapy， represented by Astragali Radix and Notoginseng Radix et Rhizoma， in treating PLGC may be through inhibiting the expression of miR216b and activating Beclin1， thus promoting autophagy and repairing gastric mucosa.
RESUMEN
Gastric cancer （GC）， originating from gastric mucosal epithelium， threatens the life and health of patients. The morbidity and mortality are high in developing countries including China. Despite the major headway in medical technology， methods such as surgery， chemotherapy， and targeted therapy fail to curb the progression. Thus， it is particularly important to clarify the etiopathogenesis and molecular mechanism of this disease and develop effective therapy. The continuous progression of GC is inseparable from the changes in the energy metabolism of tumor cells. Aerobic glycolysis （AEG）， as a unique metabolic method of tumors， directly or indirectly results in various malignant phenotypes of GC tissues. The tumor microenvironment promotes the AEG， as its disordered signaling molecules activate a large number of signaling pathways， key proteins， glycolysis-related enzymes， and various genes that initiate AEG and regulate its activity and ultimately improve the AEG level. In recent years， major progress has been made in research on the intervention of AEG in GC cells with Chinese medicinals， components of Chinese medicinals， and compound Chinese medicine prescriptions. Chinese medicine has shown multi-target and multi-pathway characteristics in the anti-GC process， thus attracting the interest of scholars in China and abroad. This study reviews the intervention of Chinese medicine in AEG of GC from the aspects of genes， proteins， key enzymes of glycolysis， and signaling pathways， in order to further clarify the exact role of AEG in the development of GC and the specific relationship of Chinese medicine with AEG and GC. In addition， the limitations of available research were summarized. This study is expected to provide a reference for future clinical and experimental research in related fields.