Insulin Resistance Reduces Sensitivity to Cis-Platinum and Promotes Adhesion, Migration and Invasion in HepG2 Cells
| Autor: | Bei Wang, Bei Xie, Jing Chen, Hu-Lai Wei, Cai-Li Li, Fei Li, Yu-Mei Liu, Guang-Di Li, Lin-Jing Li |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
medicine.medical_specialty Carcinoma Hepatocellular Epidemiology medicine.medical_treatment Down-Regulation Antineoplastic Agents Biology Carbohydrate metabolism Insulin resistance Downregulation and upregulation Cell Movement Cell Line Tumor Internal medicine Cell Adhesion medicine Humans Hypoglycemic Agents Insulin Neoplasm Invasiveness Cell Proliferation Glucose Transporter Type 2 Pioglitazone Liver Neoplasms Public Health Environmental and Occupational Health Hep G2 Cells medicine.disease Receptor Insulin Insulin receptor Glucose Endocrinology Liver Oncology Drug Resistance Neoplasm Cell culture Cancer cell Cancer research biology.protein Thiazolidinediones Cisplatin Insulin Resistance Neoplasm Recurrence Local Energy Metabolism medicine.drug |
| Zdroj: | Asian Pacific Journal of Cancer Prevention. 15:3123-3128 |
| ISSN: | 1513-7368 |
| DOI: | 10.7314/apjcp.2014.15.7.3123 |
| Popis: | The liver is normally the major site of glucose metabolism in intact organisms and the most important target organ for the action of insulin. It has been widely accepted that insulin resistance (IR) is closely associated with postoperative recurrence of hepatocellular carcinoma (HCC). However, the relationship between IR and drug resistance in liver cancer cells is unclear. In the present study, IR was induced in HepG2 cells via incubation with a high concentration of insulin. Once the insulin-resistant cell line was established, the instability of HepG2/ IR cells was further tested via incubation in insulin-free medium for another 72h. Afterwards, the biological effects of insulin resistance on adhesion, migration, invasion and sensitivity to cis-platinum (DDP) of cells were determined. The results indicated that glucose consumption was reduced in insulin-resistant cells. In addition, the expression of the insulin receptor and glucose transportor-2 was downregulated. Furthermore, HepG2/IR cells displayed markedly enhanced adhesion, migration, and invasion. Most importantly, these cells exhibited a lower sensitivity to DDP. By contrast, HepG2/IR cells exhibited decreased adhesion and invasion after treatment with the insulin sensitizer pioglitazone hydrochloride. The results suggest that IR is closely related to drug resistance as well as adhesion, migration, and invasion in HepG2 cells. These findings may help explain the clinical observation of limited efficacy for chemotherapy on a background of IR, which promotes the invasion and migration of cancer cells. |
| Databáze: | OpenAIRE |
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