title: Targeted blockade of interleukin-8 abrogates its promotion of cervical cancer growth and metastasis.
abstract: Surgery and radiotherapy have been used for decades to treat cervical cancer; however, high recurrence and lymph node metastasis rates are observed after these procedures. New therapeutic agents are needed to improve survival rates of patients by reducing tumor growth and metastasis. We previously demonstrated that interleukin-8 (IL-8) was associated with lymph node metastasis of early cervical squamous cell carcinoma (SCC). The current study assessed the role of IL-8 in growth and metastasis of cervical SCC and evaluated the effects of targeting IL-8 with small hairpin RNA (shRNA) and a human anti-IL-8 antibody. The human cervical SCC cell lines CaSki (high IL-8 producers), SiHa, HeLa, and SiHa transfected with the IL-8 gene were used for the studies. IL-8 stimulated proliferation, migration, and invasion but prevented apoptosis of SCC cells in vitro. Suppressing IL-8 expression with shRNA reduced cell growth and invasion of SCC cells in vitro. In a xenograft model, SCC cells were inoculated subcutaneously into athymic mice to evaluate the effect of IL-8 and its antibody on tumor growth and metastasis and animal survival. IL-8 enhanced tumor growth and metastasis in vivo concomitant with reduced animal survival. IL-8 antibody treatment of tumor-bearing animals resulted in smaller tumor volume, decreased lymph node metastasis, and longer animal survival. Blockade of IL-8 with an antibody demonstrated significant anti-tumor effects in a xenograft model and may thus provide a potential alternative approach for the treatment of cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Shanxi Academy of Medical Sciences & Shanxi Dayi Hospital, Taiyuan, 030032 Shanxi, China. suhuiwu@126.com
authors.forename: Suhui
authors.initials: S
authors.lastname: Wu
authors.forename: Haixia
authors.initials: H
authors.lastname: Shang
authors.forename: Lihuan
authors.initials: L
authors.lastname: Cui
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Ren-Ke
authors.initials: RK
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D016209:Interleukin-8; D034741:RNA, Small Interfering; D019938:Cyclin D1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9