Oblongifolin C reverses GEM resistance via suppressing autophagy flux in bladder cancer cells.

Abstract

A number of previous studies have demonstrated that inhibiting autophagy can increase the cellular cytotoxicity of chemotherapeutic agents in urothelial cancer cells. However, the mechanistic roles of autophagy in gemcitabine (GEM) resistant bladder cancer cells have not been thoroughly investigated. In the present study, immunohistochemistry staining of autophagy marker LC3 was performed in bladder cancer and healthy control tissues and demonstrated an essential role of autophagy in cancer development. A GEM-resistant cell line was established to assess the effects of autophagy on the acquisition of GEM resistance. Western blotting of autophagy markers in GEM-resistant bladder cancer cells suggested that GEM resistance was caused, at least partially, by GEM-induced autophagy. GEM resistance was demonstrated to be reversed by the inhibition of autophagy by 3-methyladenine. In addition, oblongifolin C (OC), a novel autophagic flux inhibitor purified from traditional Chinese medicine, was found to enhance the efficiency of GEM in GEM-resistant bladder cancer cells by inhibiting autophagic flux. In conclusion, data from the present study suggest that autophagy serves an important role in bladder cancer development and GEM resistance. OC treatment has the ability to reverse GEM-resistance in bladder cancer cells by suppressing autophagic flux, thereby providing a potential adjunctive therapeutic option for bladder cancer GEM treatment.