Research Paper Volume 13, Issue 10 pp 14289—14303

Autophagy deficiency downregulates O6methylguanine-DNA methyltransferase and increases chemosensitivity of liver cancer cells

Autophagy deficiency-induced MGMT depletion promotes cytotoxicity. (A) Cell death assessed by flow cytometry (FC) in ctrl-shRNA and sh-Atg5 HepG2 cells overexpressing MGMT, and treated with epirubicin (4 μM) for 24 h. (B) Cell death FC analysis of TMZ (200 μM; 24 h)-treated ctrl-shRNA and sh-Atg5 transfected HepG2 cells overexpressing MGMT. (C, D) Cell death analyzed by FC in HepG2 cells transfected with lentivirus Atg7-shRNA or control vector, overexpressing MGMT, and treated with epirubicin and TMZ. (E, F) CQ was used to inhibit autophagy in HepG2 and Huh7 cells. Cell death was analyzed by FC. HepG2 and Huh7 cells were transfected with MGMT overexpression plasmid, and further exposed to 4 μM of epirubicin for 24 h in the absence and presence of CQ. Data are presented as the mean ±SD (* P≤0.05; ** P≤0.01).

Figure 4. Autophagy deficiency-induced MGMT depletion promotes cytotoxicity. (A) Cell death assessed by flow cytometry (FC) in ctrl-shRNA and sh-Atg5 HepG2 cells overexpressing MGMT, and treated with epirubicin (4 μM) for 24 h. (B) Cell death FC analysis of TMZ (200 μM; 24 h)-treated ctrl-shRNA and sh-Atg5 transfected HepG2 cells overexpressing MGMT. (C, D) Cell death analyzed by FC in HepG2 cells transfected with lentivirus Atg7-shRNA or control vector, overexpressing MGMT, and treated with epirubicin and TMZ. (E, F) CQ was used to inhibit autophagy in HepG2 and Huh7 cells. Cell death was analyzed by FC. HepG2 and Huh7 cells were transfected with MGMT overexpression plasmid, and further exposed to 4 μM of epirubicin for 24 h in the absence and presence of CQ. Data are presented as the mean ±SD (* P≤0.05; ** P≤0.01).