title: The role of Bax and Bcl-2 in gemcitabine-mediated cytotoxicity in uveal melanoma cells.
abstract: Gemcitabine (GEM), a new cytotoxic agent, was shown to be effective against uveal melanoma (UM) which is noted for its resistance to chemotherapy. In this study, we found the different sensitivities to GEM in UM cell lines and identified apoptotic cell death as the cause of GEM cytotoxicity. Both UM cell lines showed an increase in Bax protein levels and activation of cleaved Caspase 3. Additionally, SP6.5 cells showed a gradual increase in Bcl-2 expression over time, whereas VUP cells showed almost none. After interfering in the expression of Bcl-2, the sensitivity to GEM was obviously enhanced in SP6.5 cells. These results suggest that an increase in Bax plays a crucial role in apoptotic cell death induced by GEM in the absence of p53. Moreover, inhibition of Bcl-2 expression can efficiently enhance the cytotoxic effect of, and sensitivity to, GEM in UM cells.
authors.affiliation: Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Renbing
authors.initials: R
authors.lastname: Jia
authors.forename: Yidan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.forename: Yixiong
authors.initials: Y
authors.lastname: Zhou
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism; D000093542:Gemcitabine; D000098943:Uveal Melanoma
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D003841:Deoxycytidine; D053148:Caspase 3; D000093542:Gemcitabine