Serum immunoglobulin fused interferon-alpha inhibited tumor growth in athymic mice bearing colon 26 adenocarcinoma cells.
Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 x : 30 microg/kg and 50 x : 150 microg/kg). A slight anti-tumoral effect was observed in all 10 x groups compared to the control. In the 50 x groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-beta. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition.
Kim
Jun-Sung
JS
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 1510-742, Korea.
Yu
Kyeong Nam
KN
Noh
Mi Suk
MS
Woo
Min-Ah
MA
Park
Sung-Jin
SJ
Park
Jin Hong
JH
Hua
Jin
J
Cho
Hyun Sun
HS
Hwang
Soon Kyung
SK
Lee
Eun-Sun
ES
Chung
Youn-Sun
YS
Choi
In-Young
IY
Kwon
Se-Chang
SC
Cho
Myung-Haing
MH
D000230:Adenocarcinoma / Q000188:drug therapy*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001806:Blood Urea Nitrogen; D004305:Dose-Response Relationship, Drug; D007136:Immunoglobulins / Q000737:chemistry* / Q000494:pharmacology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D007136:Immunoglobulins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a