Combination of human Fas (CD95/Apo-1) ligand with adriamycin significantly enhances the efficacy of antitumor response.
The prognosis of hepatocellular carcinoma (HCC) is poor, even with the combined treatment of curative resection and adjuvant chemoradiotherapy. To solve this problem, many biologic therapies have been investigated. Fas ligand (FasL, CD95L) is mainly expressed in activated T lymphocytes and natural killer (NK) cells, and plays a central role in both cell-mediated immunity and immune downregulation. Several studies have shown that FasL is expressed in HCC. In the present report, we prepared recombinant human pET-22b(+)/FasL protein and investigated the effect of FasL on HCC cells in vitro and on tumor growth in a murine HCC tumor model. The well-known cytotoxic chemotherapeutic reagent adriamycin (ADM) served as a control. We found that FasL effectively suppressed the viability of H22 tumor cells and significantly induced the apoptosis of H22 cells. The apoptotic levels of cells treated with FasL-ADM were significantly higher than those treated with FasL or ADM alone, and the FasL-ADM combination resulted in a more than additive effect on tumor growth delay in this model. The results suggested that combined treatment of FasL and other chemotherapeutic agents may be a new approach to improve the efficacy of chemotherapy for HCC.
Liu
Zhongchen
Z
Anti-Cancer Research Center, Medical College, Xiamen University, 422 Siming South Road, Xiamen, Fujian 361005, China.
Liu
Ruizhen
R
Qiu
Jinhua
J
Yin
Ping
P
Luo
Fanghong
F
Su
Jinhua
J
Li
Wenzhu
W
Chen
Caixia
C
Fan
Xin
X
Zhang
Jiakai
J
Zhuang
Guohong
G
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D053222:Fas Ligand Protein / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D053222:Fas Ligand Protein; D011994:Recombinant Proteins; D004317:Doxorubicin