title: Autophagy in human skin squamous cell carcinoma: Inhibition by 3-MA enhances the effect of 5-FU-induced chemotherapy sensitivity.
abstract: Autophagy is an intracellular multi-step catabolic degradation process that involves the degradation and recycling of cellular proteins and cytoplasmic damaged organelles to maintain cellular homeostasis and reduction of metabolic stress. Numerous studies have indicated the importance of autophagy in cancer, but the role of autophagy in human skin squamous cell carcinoma (SSCC) development and response to therapy it is still unclear. In the present study, we investigated the role of autophagy in SSCC and the relationship with chemotherapy sensitivity. The present study demonstrated that autophagy related gene the microtubule-associated protein 1 light chain 3 (LC3) expression was low in SSCC. The negative correlation with Bcl2 and survivin, and the chemotherapy drug 5-FU increased the level of autophagy and the autophagy inhibitor 3-MA inhibited this effect in SSCC cells, time- and dose-dependently. When SSCC cells were treated first with 3-MA and then with 5-FU, the inhibition of proliferation, migration, invasion and apoptosis of SSCC cells was enhanced. Our results suggested the possibility of autophagy as a potential target in SSCC therapy and 3-MA and 5-FU combination treatment may be an effective SSCC therapy via autophagy modulating.
authors.affiliation: Department of Dermatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology Anatomy, Medicine School of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; C025946:3-methyladenine; D000225:Adenine; D005472:Fluorouracil