Abstract:Objective To reveal the effect of deoxydebilirubin (DET) on autophagy and mammalian target of rapamycin (mTOR) signaling pathway in lung cancer cells. Methods After treatment of human non-small cell lung cancer cell line (A549) with different concentrations of DET (0 μM, 5 μM, 10 μM, 20 μM and 50 μM), cell viability was detected by tetramethylazolium salt (MTT), apoptosis was detected by flow cytometry, and cell migration and invasion were detected by Transwell. The protein expressions of Beclin-1, microtubule associated protein 1 light chain 3 (LC3), mTOR, p-mTOR, p70 ribosomal S6 protein kinase (P70S6K), p-P70S6K, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and p-4E-BP1 were detected by Western blot. Nude mice transplanted with A549 cells were randomly divided into Control group(n=6)and DET group (n=6). The mice in DET group were intraperitoneally injected with DET solution (10 mg/kg), and the mice in Control group were injected intraperitoneally with normal saline containing 1% DMSO. After 21 days of administration, the tumor volume and weight of the two groups of nude mice were detected respectively. The protein expressions of p-mTOR, p-p70S6K and p-4E-BP1 in tumor tissues were detected by immunohistochemistry. Results Compared with 0 μM, the growth inhibition rate and apoptosis rate of A549 cells treated with 5 μM, 10 μM, 20 μM and 50 μM DET increased, the number of migratory and invasive cells decreased (P<0.05), the relative expression of Beclin-1 and LC3-Ⅱ/LC3-Ⅰ increased, the relative expression of p-mTOR/mTOR, p-p70S6K/ p70S6K and p-4E-BP1/4E-BP1 decreased (P<0.05). Compared with Control, the volume and weight of tumor in DET group decreased, and the staining scores of p-mTOR, p-p70S6K and p-4E-BP1 in tumor tissue decreased (P<0.05). Conclusion The anti-lung cancer effect of DET may be related to its inhibition of mTOR signaling pathway and induction of autophagy in lung cancer cells