Geridonin and paclitaxel act synergistically to inhibit the proliferation of gastric cancer cells through ROS-mediated regulation of the PTEN/PI3K/Akt pathway
Metrics: PDF 2874 views | HTML 2479 views | ?
Sai-Qi Wang1,*, Cong Wang1,*, Li-Ming Chang1, Kai-Rui Zhou1, Jun-Wei Wang1, Yu Ke1, Dong-Xiao Yang1, Hong-Ge Shi1, Ran Wang1, Xiao-Li Shi1, Li-Ying Ma1, Hong-Min Liu1
1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, P.R. China
*These authors contributed equally to this work
Hong-Min Liu, email: [email protected]
Keywords: gastric cancer, paclitaxel resistance, oridonin, synergism, PI3K/Akt pathway
Received: April 12, 2016 Accepted: September 02, 2016 Published: September 21, 2016
Paclitaxel, a taxane, is a cytotoxic chemotherapeutic agent that targets microtubules. It has become a front-line therapy for a broad range of malignancies, including lung, breast, gastric, esophageal, and bladder carcinomas. Although paclitaxel can inhibit tumor development and improve survival, poor solubility, myelotoxicity, allergic reactions, and drug resistance have restricted its clinical application. Paclitaxel is frequently combined with other chemotherapeutics to enhance the antitumor effects and reduce side effects. We synthesized geridonin, a derivative of oridonin, and demonstrate that geridonin and paclitaxel act synergistically to inhibit the growth of gastric cancer cells. Importantly, geridonin enhanced the antitumor effects of paclitaxel without increasing toxicity in vivo. Mechanistic analysis revealed that administration of geridonin in combination with paclitaxel up-regulated the tumor suppressor PTEN and inhibited phosphorylation of Akt and MDM2. This led to the accumulation of p53 and induced apoptosis though the mitochondrial pathway. Thus, geridonin in combination with paclitaxel is a new treatment strategy for gastric cancer.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.