title: Insulin resistance reduces sensitivity to Cis-platinum and promotes adhesion, migration and invasion in HepG2 cells.
abstract: 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.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China E-mail : weihulai@lzu.edu.cn.
authors.forename: Lin-Jing
authors.initials: LJ
authors.lastname: Li
authors.forename: Guang-Di
authors.initials: GD
authors.lastname: Li
authors.forename: Hu-Lai
authors.initials: HL
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Bei
authors.initials: B
authors.lastname: Xie
authors.forename: Bei
authors.initials: B
authors.lastname: Wang
authors.forename: Cai-Li
authors.initials: CL
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000096:biosynthesis; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D000077205:Pioglitazone; D011972:Receptor, Insulin / Q000096:biosynthesis; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D011972:Receptor, Insulin; D005947:Glucose; D002945:Cisplatin; D000077205:Pioglitazone