The antitumor activity of recombinant antitumor antiviral protein and the associated molecular mechanism in pancreatic tumor cells.
BACKGROUND
Pancreatic cancer has poor prognosis and high mortality. Currently, the therapy of pancreatic cancer remains a challenge. In this study, we compared the antitumor activity of the recombinant antitumor antiviral protein (RAAP), an improved interferon, with gemcitabine, a classic chemotherapy agent used for pancreatic cancer treatment.


METHODS
The proliferation of Bx-PC3 pancreatic cancer cells was evaluated by an MTT assay. Cell cycle arrest and apoptosis were evaluated by flow cytometry and annexin V-FITC/propidium iodide double staining, respectively. The expressions of matrix metalloproteinase (MMP)-2, MMP-9, caspase-3, caspase-8, and caspase-9 genes were evaluated by reverse transcription-polymerase chain reaction and the Western blot analysis. A xenograft pancreatic cancer model was established by inoculating Bx-PC3 cells into athymic nude mice. The antitumor activity of RAAP and gemcitabine was tested in the xenograft tumor model.


RESULTS
RAAP significantly inhibited proliferation, induced cell cycle arrest, and induced apoptosis in Bx-PC3 cells in vitro and delayed tumor growth in vivo. The antitumor activity of 20 ng/mL of RAAP was a little more effective than 10 μM of gemcitabine. The antitumor activity of RAAP was associated with its role in inducing caspase-3 and caspase-8 expression as well as downregulating MMP-2 expression.


CONCLUSIONS
RAAP can effectively suppress human pancreatic cancer cell growth in vitro and in vivo. The antitumor efficacy of RAAP is similar to gemcitabine.
Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, P.R. China.
Jie
J
Zeng
Ying
Y
Xiong
Long-Bo
LB
Zhang
Jing-de
JD
Ruan
Wei
W
Wu
Wei-Jia
WJ
Sun
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D003841:Deoxycytidine; D007372:Interferons; D000093542:Gemcitabine