Geridonin and paclitaxel act synergistically to inhibit the proliferation of gastric cancer cells through ROS-mediated regulation of the PTEN/PI3K/Akt pathway
| Autor: | Dongxiao Yang, Jun-Wei Wang, Sai-Qi Wang, Xiaoli Shi, Hong-Min Liu, Yu Ke, Li-Ying Ma, Cong Wang, Ran Wang, Hongge Shi, Liming Chang, Kairui Zhou |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Paclitaxel Antineoplastic Agents Apoptosis Pharmacology Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Stomach Neoplasms synergism Cell Line Tumor Animals Humans Medicine PTEN Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Membrane Potential Mitochondrial Taxane biology business.industry gastric cancer PTEN Phosphohydrolase Cancer Drug Synergism medicine.disease Xenograft Model Antitumor Assays paclitaxel resistance Disease Models Animal 030104 developmental biology Oncology chemistry PI3K/Akt pathway 030220 oncology & carcinogenesis Cancer cell oridonin biology.protein Diterpenes Kaurane Reactive Oxygen Species business Proto-Oncogene Proteins c-akt Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.12166 |
| Popis: | // Sai-Qi Wang 1, * , Cong Wang 1, * , Li-Ming Chang 1 , Kai-Rui Zhou 1 , Jun-Wei Wang 1 , Yu Ke 1 , Dong-Xiao Yang 1 , Hong-Ge Shi 1 , Ran Wang 1 , Xiao-Li Shi 1 , Li-Ying Ma 1 , Hong-Min Liu 1 1 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, P.R. China * These authors contributed equally to this work Correspondence to: Hong-Min Liu, email: liuhm@zzu.edu.cn Keywords: gastric cancer, paclitaxel resistance, oridonin, synergism, PI3K/Akt pathway Received: April 12, 2016 Accepted: September 02, 2016 Published: September 21, 2016 ABSTRACT 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. |
| Databáze: | OpenAIRE |
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