Drug Design, Development and Therapy (Feb 2023)
Solanine Represses Gastric Cancer Growth by Mediating Autophagy Through AAMDC/MYC/ATF4/Sesn2 Signaling Pathway
Abstract
Xiaolong Tang,1,2,* YingYing Guo,2,* Sijia Zhang,2 Xin Wang,2 Yuhao Teng,3 Qingjiang Jin,2 Qinglei Jin,2 Wei Shen,2,* Ruiping Wang1,3,* 1The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2Department of Oncology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China; 3Department of Oncology, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Shen, Department of Oncology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 39 Xiashatang Road, Wuzhong District, Suzhou, Jiangsu, People’s Republic of China, Email [email protected] Ruiping Wang, Department of Oncology, the Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu, People’s Republic of China, Tel +13815883181, Email [email protected]: Solanine is the main component of the plant Solanum, which has been shown to provide growth-limiting activities in a variety of human cancers. However, little is known about its function in gastric cancer (GC).Methods: We investigated the effect of solanine on GC in vivo and in vitro. The inhibition rate of solanine on the tumor was observed by constructing a subcutaneous tumor in nude mice. Morphological changes were analyzed with H&E staining. The expression of ATF4 was detected by IF analysis. MTT assays, EdU staining, and colony formation assays were used to detect the inhibition rate of solanine on GC cells. Matrigel transwells were used to detect the invasion of GC cells. Cell migration was measured using the wound healing assay. The flow cytometric analysis was used to monitor changes in the cell cycle and cell apoptosis. Western blotting was used to detect major proteins in cells and tumors.Results: Solanine suppressed gastric tumorigenesis. Solanine also inhibited the proliferation, invasion and mitigation of GC cells, and induced cell cycle arrest and apoptosis in vitro. Moreover, the growth-limiting activities of solanine in gastric cancer were related to the suppression of the AAMDC/MYC/ATF4/Sesn2 pathway-mediated autophagy. Overexpression of AAMDC reversed the inhibitory effect of solanine on autophagy and gastric cancer.Conclusion: In summary, our findings indicate that solanine confers growth-limiting activities by deactivating the AAMDC-regulated autophagy in gastric cancer.Keywords: gastric cancer, autophagy, AAMDC, solanine
