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 stability 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.

Knockdown of TMEM45A overcomes multidrug resistance and epithelial–mesenchymal transition in human colorectal cancer cells through inhibition of TGF‐β signalling pathway

“…Since MDR promotes the metastasis in various types of cancer cells, Transwell assays were performed to investigate the effects of TMEM45A knockdown on the migration and invasion of HCT‐8/5‐FU and SW480/5‐FU cells. As shown in Figure , the migratory and invasive capacities were significantly enhanced in HCT‐8/5‐FU and SW480/5‐FU cells compared with those in parental HCT‐8 and SW480 cells ( && P < .01 vs HCT‐8 or SW480 cells, Figure A‐H).…”

Overcoming 5-Fu Resistance of Colon Cells through Inhibition of Glut1 by the Specific Inhibitor WZB117

“…As a result, most cancers display upregulated glucose transport and aerobic glycolysis regardless of their oxygen status (Zhao et al, 2013;Li et al, 2014). In addition, cancer cells are found to be sensitive to glucose deprivation due to the dependence on glucose as major nutrition supply (Vander et al, 2009).…”