title: Combination of interferon-α and 5-fluorouracil induces apoptosis through mitochondrial pathway in hepatocellular carcinoma in vitro.
abstract: Many clinical reports have proven that the combination therapy of interferon-alpha plus 5-fluorouracil is remarkably effective for advanced hepatocellular carcinoma (HCC). However, the mechanism of this therapy is not well understood. Here, we demonstrated that the combination therapy synergistically inhibited the growth of Fas-negative HCC cells, arrested cell-cycle progression and induced apoptosis. Moreover, the combination therapy significantly increased the protein expression of caspase-8, activated Bid and cytochrome c. Meanwhile, the expression of anti-apoptotic gene Bcl-xL was reduced and intracellular calcium elevated obviously during the early stage of treatment. Therefore, mitochondrial pathway was involved in the apoptosis of Fas-negative HCC cells induced by IFN-α/5-FU and Ca(2+) partially promoted the beneficial effect against HCC.
authors.affiliation: Institute of Basic Medical Sciences, Qi Lu Hospital, Shandong University, Jinan, PR China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Yin
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Xie
authors.forename: Jiao
authors.initials: J
authors.lastname: Zhang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yang
authors.forename: Biping
authors.initials: B
authors.lastname: Deng
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Qu
authors.forename: Haiting
authors.initials: H
authors.lastname: Mao
mesh_terms: D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D045304:Cytochromes c / Q000378:metabolism; D018450:Disease Progression; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D016898:Interferon-alpha; D051020:bcl-X Protein; D045304:Cytochromes c; D053181:Caspase 8; D002118:Calcium; D005472:Fluorouracil