Combination treatment strategies with a focus on rosiglitazone and adriamycin for insulin resistant liver cancer

Abstract

Insulin resistance promotes the occurrence of liver cancer and decreases its chemosensitivity. Rosiglitazone (ROSI), a thiazolidinedione insulin sensitiser, could be used for diabetes with insulin resistance and has been reported to show anticancer effects on human malignant cells. In this paper, we investigated the combination of ROSI and chemotherapeutics on the growth and metastasis of insulin-resistant hepatoma. In vitro assay, ROSI significantly enhanced the inhibitory effects of adriamycin (ADR) on the proliferation, autophagy and migration of insulin-resistant hepatoma HepG2/IR cells via downregulation of EGFR/ERK and AKT/mTOR signalling pathway. In addition, ROSI promoted the apoptosis of HepG2/IR cells induced by ADR. In vivo assay, high fat and glucose diet and streptozotocin (STZ) induced insulin resistance in mice by increasing the body weight, fasting blood glucose (FBG) level, oral glucose tolerance, fasting insulin level and insulin resistance index. Both the growth of mouse liver cancer hepatoma H22 cells and serum FBG level in insulin resistant mice were significantly inhibited by combination of ROSI and ADR. Thus, ROSI and ADR in combination showed a stronger anti-tumour effect in insulin resistant hepatoma cells accompanying with glucose reduction and might represent an effective therapeutic strategy for liver cancer accompanied with insulin resistant diabetes.

Keywords:

• Insulin resistance
• HepG2/IR cells
• rosiglitazone
• adriamycin
• insulin resistant diabetes mice hepatoma model

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was funded by Natural Science Foundation of Shandong Province [ZR201911040182], Key Research and Development Program of Shandong Province [2017CXGC1401], and China Australia Centre for Health Science Research [CACHSR no. 2019GJ01].