Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma.
OBJECTIVE
To determine whether IFN-alpha is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy, we tested IFN-alpha for its synergistic properties.


METHODS
Eight pancreatic carcinoma cell lines were treated with the single agents and combinations of these. The role of IFN-alpha regarding a) direct inhibitory effects; b) radio and chemosensitizing effects; c) anti-angiogenic properties and d) enhancement of immunogenicity was investigated.


RESULTS
Our results show that IFN-alpha has direct inhibitory properties and some synergistic influence as determined by AnnexinV/PI stain and cell count. IFN-alpha is also able to prevent the increase in proliferation rate and VEGF secretion of CDDP resistant cells. Having taken the results from immunogenicity experiments together, we found cells that can be influenced by IFN-alpha but were less susceptible against T cells. Furthermore, high expression of MHC molecules, CD118, EGF-R and Fas was predictive for a good response.


CONCLUSIONS
In conclusion, IFN-alpha has direct cytotoxic effects, acts as a radiosensitizer and circumvents tumor cell-regrowth after CDDP treatment. These mechanisms may be responsible for the good clinical outcome of CapRI.
Ma
Jian-Hua
JH
Department of Surgery, Univerity of Heidelberg, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany. angela.maerten@med.uni-heidelberg.de
Patrut
Emilia
E
Schmidt
Jan
J
Knaebel
Hanns-Peter
HP
Büchler
Markus W
MW
Märten
Angela
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000627:therapeutic use*; D004357:Drug Synergism; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin