Effect of Elian Granule on Autophagy and PI3K/Akt/mTOR Signaling Pathway in Gastric Tissue of Rats with Gastric Cancer / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effect of Elian granule on autophagy and the phosphatidylinositol -3 kinase （PI3K）/protein kinase B （PKB/Akt）/mammalian target of rapamycin （mTOR） signaling pathway in gastric tissue of rats with gastric cancer. Method:SPF SD rats were randomly divided into the normal， model， Elian granule， and Weifuchun groups. In addition to the routine feeding in the normal group， the model， Elian granule， and Weifuchun groups received <italic>N</italic>-methyl-<italic>N</italic>'-nitro-<italic>N</italic>-nitrosoguanidine （MNNG） to induce gastric cancer in rats， and they were respectively given normal saline， Elian granule aqueous solution （3.240 g·kg^-1） and Weifuchun aqueous solution （0.390 g·kg^-1） by gavage （<italic>ig</italic>） for 48 weeks. The gross changes of the stomach taken by laparotomy were observed by naked eyes. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes of the gastric tissue in rats. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot （WB） were used to detect the mRNA and protein expression of microtubule-associated protein 1 light chain 3 beta （LC3B）， Beclin1， p62， PI3K， Akt， mTOR in rat gastric tissue. Result:Compared with the normal group， the model group showed gastric distension， thinner gastric wall， pale gastric mucosa， atrophied and flat folds， disordered course， and visible nodules and vegetations. Compared with the model group， the Elian granule group demonstrated alleviated gastric distension， dark gastric mucosa， reduced folds， and regular course， with the thinned gastric wall improved and granular nodules observed occasionally. According to HE staining， compared with the normal group， the model group showed crowded and disordered rat gastric glands， diverse in shape， varied cell morphology， basophilic cytoplasm， large irregular hyperchromatic nuclei， visible mitosis， and infiltrated and destroyed muscularis mucosae. While compared with the model group， the arrangement of gastric glands was regular， and a few mildly atypical cells could be observed in rats of the Elian granule group. Compared with the normal group， the model group exhibited decreased expression of LC3B and Beclin1 mRNA and protein in gastric tissue （<italic>P</italic><0.05）， and increased expression of PI3K， p62， Akt， and mTOR mRNA and protein （<italic>P</italic><0.05）. Compared with the model group， the Elian granule group showed increased expression of LC3B and Beclin1 mRNA and protein in gastric tissue （<italic>P<</italic>0.05）， and decreased expression of PI3K mRNA and p62， Akt， and mTOR mRNA and protein （<italic>P</italic><0.05）. Conclusion:Elian granule can improve the cell atypia of gastric tissue in rats with gastric cancer， and the mechanism may be related to the inhibition of the PI3K/Akt/mTOR signaling pathway to promote autophagy.