Pachymic acid promotes ferroptosis and inhibits gastric cancer progression by suppressing the PDGFRB-mediated PI3K/Akt pathway
Jinlin Nie,
Haoran Zhang,
Xiaofeng Li,
Jiawei Qin,
Jiawei Zhou,
Yuhui Lu,
Nengjia Yang,
Yanan Li,
Hailiang Li,
Cheng Li
Affiliations
Jinlin Nie
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, People's Republic of China
Haoran Zhang
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, People's Republic of China
Xiaofeng Li
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China
Jiawei Qin
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China
Jiawei Zhou
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China
Yuhui Lu
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China
Nengjia Yang
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China
Yanan Li
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China
Hailiang Li
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China; Corresponding author. The Affiliated Guangdong Second Provincial General Hospital of Jinan University, 466 Middle Xingang Road, Guangzhou, 510317, Guangdong, People's Republic of China.
Cheng Li
Department of Hepatobiliary Pancreatic Hernia Surgery, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, People's Republic of China; Corresponding author. The Affiliated Guangdong Second Provincial General Hospital of Jinan University, 466 Middle Xingang Road, Guangzhou, 510317, Guangdong, People's Republic of China.
Gastric cancer (GC) is a common malignant tumour with high incidence and mortality rates worldwide. Despite current treatment modalities, including surgical resection and chemotherapy, challenges such as postoperative recurrence, metastasis and drug resistance persist. Therefore, investigating the feasibility and mechanism of traditional Chinese medicine in treating gastric cancer is crucial for discovering new anti-gastric cancer drugs or adjuvant therapies. Pachymic acid (PA) is a natural triterpenoid found in the traditional Chinese medicinal herb Poria cocos (PC) (Schw. Wolf). Recent studies have reported its inhibitory effects on various cancer cells, including liver, cervical, breast and gastric cancer. Our in vitro and in vivo experiments confirmed that PA inhibits the proliferation, migration and invasion of gastric cancer cells. The treatment of gastric cancer cells with various death inhibitors revealed that PA may suppress gastric cancer progression by inducing ferroptosis. Malondialdehyde, Fe2+, reactive oxygen species and glutathione assays were performed to validate the effects of PA on ferroptosis in gastric cancer. High-throughput sequencing combined with analysis of the TCGA database identified PDGFRB as a potential downstream target of PA. In vivo experiments indicated that the PDGFRB overexpression could counteract the antitumour effects of PA, while ferroptosis induced by the PI3K/Akt signalling pathway may play a key role in this process. This study provides initial evidence that PA, through its interaction with PDGFRB, alters the PI3K/Akt signalling pathway, leading to ferroptosis in gastric cancer cells, thus manifesting its antitumour properties. This discovery holds promise for the development of novel therapeutic strategies for gastric cancer patients.
