Synergistic Antitumor Effect of Doxorubicin and Tacrolimus (FK506) on Hepatocellular Carcinoma Cell Lines

被引：15

作者：

Capone, Francesca ^{[1
]}

Guerriero, Eliana ^{[1
]}

Sorice, Angela ^{[1
]}

Colonna, Giovanni ^{[2
]}

Storti, Gabriella ^{[3
]}

Pagliuca, Jessica ^{[1
]}

Castello, Giuseppe ^{[1
]}

Costantini, Susan ^{[1
]}

机构：

[1] IRCCS, Ist Nazl Studio & Cura Tumori Fdn Giovanni Pascal, I-80131 Naples, Italy

[2] Univ Naples 2, Biochem Biophys & Gen Pathol Dept, I-80138 Naples, Italy

[3] SG Moscati Hosp, Dept Oncohematol, I-83100 Avellino, Italy

来源：

SCIENTIFIC WORLD JOURNAL | 2014年

关键词：

SERUM CYTOKINE LEVELS; EXPRESSION; AUTOPHAGY; TUMOR; INHIBITION; APOPTOSIS; COMBINATION; SORAFENIB; NECROSIS;

D O I：

10.1155/2014/450390

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hepatocellular carcinoma is the fifth most common cancer worldwide and shows a complex clinical course, poor response to pharmacological treatment, and a severe prognosis. Thus, the aim of this study was to investigate whether tacrolimus (FK506) has synergistic antitumor effects with doxorubicin on two human hepatocellular carcinoma cell lines, Huh7 and HepG2. Cell viability was analyzed by Sulforhodamine B assay and synergic effect was evaluated by the software CalcuSyn. Cell apoptosis was evaluated using Annexin V and Dead Cell assay. Apoptosis-related protein PARP-1 cleaved and autophagy-related protein expressions (Beclin-1 and LC3B) were measured by western blotting analysis. Cytokines concentration in cellular supernatants after treatments was studied by Bio-Plex assay. Interestingly the formulation with doxorubicin and tacrolimus induced higher cytotoxicity level on tumor cells than single treatment. Moreover, our results showed that the mechanisms involved were (i) a strong cell apoptosis induction, (ii) contemporaneous decrease of autophagy activation, understood as prosurvival process, and (iii) downregulation of proinflammatory cytokines. In conclusion, future studies could relate to the doxorubicin/tacrolimus combination effects in mice models bearing HCC in order to see if this formulation could be useful in HCC treatment.

引用

页数：9

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