Xinyu Li1, Wen Chen2, Jing Jia1, Chunkang Yang3, Yisen Huang1, Rongyu Xu4, Shen Guan5, Ruijun Ma6, Haitao Yang7, Lifeng Xie1. 1. Department of Gastrointestinal Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou City, 362002, Fujian Province, China. 2. Department of Traditional Chinese Medicine Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou City, 362000, Fujian Province, China. 3. Department of Gastrointestinal Surgery, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, 420 Fuma Road, Jin'an District, Fuzhou City, 350005, Fujian Province, China. lixy@fjmu.edu.cn. 4. Department of Thoracic Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou City, 362002, Fujian Province, China. 274272615@qq.com. 5. Department of Gastrointestinal Surgery, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, 420 Fuma Road, Jin'an District, Fuzhou City, 350005, Fujian Province, China. 6. Department of General Surgery, Tongxin County People's Hospital, Ningxia Hui Autonomous Region, Wuzhong City, 751300, Tongxin County, China. 7. Department of General Surgery, Wuzhong People's Hospital, Ningxia Hui Autonomous Region, Wuzhong City, 751000, China.
Abstract
BACKGROUND: Despite current advances in gastric cancer treatment, disease metastasis and chemo-resistance remain as major hurdles against better overall prognosis. Previous studies indicated that IGHG1 as well as -Catenin serve as important regulators of tumor cellular malignancy. Therefore, understanding detailed molecular mechanism and identifying druggable target will be of great potentials in future therapeutic development. METHODS: Surgical tissues and gastric cancer cell lines were retrieved to evaluate IGHG1 expression for patients with or without lymph node/distal organ metastasis. Functional assays including CCK8 assay, Edu assay, sphere formation assay and transwell assay, wound healing assay, etc. were subsequently performed to evaluate the impact of IGHG1/-catenin axis on tumor cell proliferation, migration and chemo-resistance. RESULTS: Gastric cancer tissues and tumor cell lines demonstrated significantly higher level of IGHG1. Functional study further demonstrated that IGHG1 promoted proliferative and migration as well as chemo-resistance of gastric cancer tumor cells. Further experiments indicated that IGHG1 activated AKT/GSK-3/-Catenin axis, which played crucial role in regulation of proliferative and chemo-resistance of gastric cancer cells. CONCLUSION: This study provided novel evidences that IGHG1 acted as oncogene by promotion of gastric cancer cellular proliferation, migration and chemo-resistance. Our research further suggested that IGHG1/AKT/GSK-3β/β-Catenin axis acted as novel pathway which regulated gastric cancer cellular malignant behavior. Our research might inspire future therapy development to promote overall prognosis of gastric cancer patients.
BACKGROUND: Despite current advances in gastric cancer treatment, disease metastasis and chemo-resistance remain as major hurdles against better overall prognosis. Previous studies indicated that IGHG1 as well as -Catenin serve as important regulators of tumor cellular malignancy. Therefore, understanding detailed molecular mechanism and identifying druggable target will be of great potentials in future therapeutic development. METHODS: Surgical tissues and gastric cancer cell lines were retrieved to evaluate IGHG1 expression for patients with or without lymph node/distal organ metastasis. Functional assays including CCK8 assay, Edu assay, sphere formation assay and transwell assay, wound healing assay, etc. were subsequently performed to evaluate the impact of IGHG1/-catenin axis on tumor cell proliferation, migration and chemo-resistance. RESULTS:Gastric cancer tissues and tumor cell lines demonstrated significantly higher level of IGHG1. Functional study further demonstrated that IGHG1 promoted proliferative and migration as well as chemo-resistance of gastric cancer tumor cells. Further experiments indicated that IGHG1 activated AKT/GSK-3/-Catenin axis, which played crucial role in regulation of proliferative and chemo-resistance of gastric cancer cells. CONCLUSION: This study provided novel evidences that IGHG1 acted as oncogene by promotion of gastric cancer cellular proliferation, migration and chemo-resistance. Our research further suggested that IGHG1/AKT/GSK-3β/β-Catenin axis acted as novel pathway which regulated gastric cancer cellular malignant behavior. Our research might inspire future therapy development to promote overall prognosis of gastric cancerpatients.
Authors: F Gulli; U Basile; L Gragnani; C Napodano; K Pocino; L Miele; S A Santini; A L Zignego; A Gasbarrini; G L Rapaccini Journal: Eur Rev Med Pharmacol Sci Date: 2018-09 Impact factor: 3.507