Interleukin-2 inhibits proliferation of HPV-associated tumor cells and halts tumor growth in vivo.
Previous studies have shown inhibition of cervical cancer cell growth by treatment with high concentrations of IL-2. In the present study, we evaluated the in vitro and in vivo effects of recombinant human IL-2 on HPV-associated tumor cells (3T3-16). Treatment of 3T3-16 cells with rhIL-2 for 72 h inhibited cell growth in a dose-dependent manner and this effect was evidenced at nanomolar concentrations. These tumor cells expressed mRNA for beta and gamma subunits of the IL-2 receptor, which are required for signal transduction. In experiments to explore the effect of IL-2 on the growth of the HPV-associated tumor, mice received rhIL-2 through different routes: (i) intraperitoneal; (ii) subcutaneous, at the tumor inoculation site; or (iii) subcutaneous, distant from the tumor inoculation site. An effective antitumor response was observed only in those animals that received IL-2 at the tumor site (P<0.01). These results indicate the potential adequacy of therapeutic strategies based on local administration of rhIL-2 for cervical carcinoma, not only based on the ability of this cytokine to stimulate cellular-mediated immunity but also because of its direct effects on tumor cells.
Casana
Patricia H
PH
Center for Genetic Engineering and Biotechnology, Havana, Cuba. patriciah@cqf.co.cu
Hernandez
Hector
H
Arana
Manuel J
MJ
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism / Q000627:therapeutic use*; D053646:Interleukin-2 Receptor beta Subunit; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D014412:Tumor Virus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; C508020:IL2RB protein, human; C508022:Il2rb protein, mouse; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2