title: Alpha fetoprotein antagonizes apoptosis induced by paclitaxel in hepatoma cells in vitro.
abstract: Hepatocellular carcinoma (HCC) cell resistance to the effects of paclitaxel has not been adequately addressed. In this study, we found that paclitaxel significantly inhibited the viability of HLE, Bel 7402 and L-02 cells in a dose- and time-dependent manner. HLE cells and L-02 cells resisted the cytotoxicity of paclitaxel when transfected with pcDNA3.1-afp vectors. However, Bel 7402 cell sensitivity to paclitaxel was increased when transfected with alpha fetoprotein (AFP)-siRNA. Bel 7402 cell resistance to paclitaxel was associated with the expression of the "stemness" markers CD44 and CD133. Paclitaxel significantly inhibited growth and promoted apoptosis in HLE cells and L-02 cells by inducing fragmentation of caspase-3 and inhibiting the expression of Ras and Survivin, but pcDNA3.1-afp vectors prevented these effects. However, paclitaxel could not significantly promote the cleavage of caspase-3 or suppress the expression of Ras and Survivin in Bel 7402 cells. Silenced expression of AFP may be synergistic with paclitaxel to restrain proliferation and induce apoptosis, enhance cleavage of caspase-3, and suppress the expression of Ras and Survivin. Taken together, AFP may be an important molecule acting against paclitaxel-inhibited proliferation and induced apoptosis in HCC cells via repressing the activity of caspase-3 and stimulating the expression of Ras and Survivin. Targeted inhibition of AFP expression after treatment with paclitaxel is an available strategy for the therapy of patients with HCC.
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.|Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571159, P.R. China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.|Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571159, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.|Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571159, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.|Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571159, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Dong
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.|Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571159, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.|Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571159, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.|Department of Pathophysiology, Hainan Medical College, Haikou 571199, China.
authors.forename: Xieju
authors.initials: X
authors.lastname: Xie
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.
authors.forename: Junli
authors.initials: J
authors.lastname: Guo
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou 571199, P.R. China.|Key Laboratory of Molecular Biology, Hainan Medical College, Haikou 571159, P.R. China.|Institution of Tumours, Hainan Medical College, Haikou 570102, P.R. China.
authors.forename: Mengsen
authors.initials: M
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053478:Apoptosomes / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D000077022:Survivin; D000509:alpha-Fetoproteins / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053478:Apoptosomes; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D000509:alpha-Fetoproteins; C505407:CASP3 protein, human; D053148:Caspase 3; D018631:ras Proteins; D017239:Paclitaxel