Trichosanthin enhances the antitumor effect of gemcitabine in non-small cell lung cancer via inhibition of the PI3K/AKT pathway.

Gemcitabine (GEMZ) is the first-line therapy used against non-small cell lung cancer (NSCLC), and studies have focused on investigating the potential effects of agents combined with GEMZ to enhance the anticancer efficacy in NSCLC. Previous studies have reported that trichosanthin (TCS) has various physiological and pharmacological effects, including anti-human influenza virus enzymes, inhibition of protein synthesis and antitumor activity. The purpose of the present study was to investigate if TCS enhanced the antitumor effects of GEMZ in NSCLC. MTT assay demonstrated that TCS significantly enhanced the cytotoxic effect of GEMZ (P>0.05). Furthermore, a propidium iodide/Αnnexin V staining assay revealed that TCS exerted its pharmacological effect by increasing the apoptotic population. In addition, western blot analysis demonstrated that the combination treatment of TCS with GEMZ further decreased the expression level of phosphoinositide 3-kinase (PI3K) and AKT via regulating the expression of insulin growth factor. The results of the present study demonstrated that TCS enhanced the cytotoxic and apoptotic effects of GEMZ in A549 cells via regulating the PI3K/AKT pathway. In conclusion, these observations may provide a potential rational basis for a combination strategy for chemotherapy treatment of NSCLC.