Silencing of glutaminase 1 resensitizes Taxol-resistant breast cancer cells to Taxol.

Taxol is a front-line chemotherapeutic agent for the treatment of patients with multiple types of tumor. However, resistance to Taxol remains one of the principal causes of cancer-associated mortality. Glutamine, which is metabolized via a glutaminase (GLS)-dependent process, termed glutaminolysis, is important in cell growth and metabolism. The present study reported a novel mechanism underlying Taxol resistance in breast cancer cells. By investigating the glutamine metabolism of breast cancer cells in response to treatment with Taxol in vitro, it was observed that Taxol induced the uptake of glutamine and the expression of GLS1. Notably, Taxol-resistant cancer cells exhibited upregulation in the metabolism of glutamine and expression of GLS1. In addition, overexpression of GLS1 rendered cancer cells resistant to Taxol, indicating that GLS1 may be the therapeutic target for overcoming Taxol resistance in clinical therapeutics. The results also demonstrated that knock-down of GLS1 using small interfering RNA, resensitized the Taxol-resistant breast cancer cells to Taxol.