Inhibitory effect of anti interleukin-8 monoclonal antibodies on cervical cancer

Abstract

Objective To investigate the inhibitory effect of anti interleukin (IL)-8 monoclonal antibodies on the growth and metastasis of cervical cancer. Methods Involved cervical cells included CaSki cells with high expression of IL-8 and SiHa cell lines with IL-8 plasmid transfected (pcDNA3.1-IL-8-SiHa). Cervical cancer animal model was established on nude mice. Boyden method was used in vitro study to observe the effects of anti IL-8 antibodies on the chemotaxis of high-expressed IL-8 cervical cancer cells. The effect of antiIL-8 antibodies on the growth of cervical cancer cells and nude mice transplantation tumor was observed by the experiment in vivo through reverse transcription-polymerase chain reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA), TUNEL method. Cell line (CaSki and pcDNA3.1-IL-8-SiHa) modeled nude mice were divided into 5 groups with 5 animals in each group. The blank control group (group Ⅰ) was given the equal volume of phosphate buffer solution (PBS). Negative control group (group Ⅱ) was injected with IgG at the same volume of IgG. Treatment group (group Ⅲ) was injected with anti IL-8 antibodies at dose of 100 μg for once and intervals for once 2 days. Treatment group (group Ⅳ) was injected with anti IL-8 antibodies at dose of 500 μg for once and intervals for once 3 days. Treatment group (group V) was injected with anti IL-8 antibodies at dose of 1 000 μg for once and intervals for once 1 week. Results Experiments in vitro showed that the cell chemotaxis ability of anti IL-8 antibody in CaSki cells and pcDNA3.1-IL-8-SiHa cells was lower than that in the blank control group (CaSki cells: F = 289.6, P = 0.000; pcDNA3.1-IL-8-SiHa cells: F = 79.0, P = 0.005). Group Ⅳ was taken as the example for its best anti-tumor effect in experiments in vivo. The tumor weight in group Ⅳ was lower than that in group Ⅰ [CaSki cells: (0.172±0.031) g vs. (0.735±0.015) g, P < 0.05; pcDNA3.1-IL-8-SiHa cells: (0.400±0.029) g vs. (1.430±0.199) g, P < 0.05]. The tumor volume in group Ⅳ was less than that in group Ⅰ [CaSki cells: (0.049±0.028) cm3 vs. (0.214±0.016) cm3, P < 0.05; pcDNA3.1-IL-8-SiHa cells: (0.063±0.022) cm3 vs. (0.600±0.072) cm3, P < 0.05]. The tumor growth curve also showed that tumor growth was slow, and the time of tumor formation as well as survival time was prolonged in anti IL-8 antibody treated group. The expression of mRNA in IL-8 in group IV was lower than that in group Ⅰ (CaSki cells: 0.58±0.06 vs. 1.15±0.13, P < 0.05; pcDNA3.1-IL-8-SiHa cells: 0.69±0.08 vs. 1.16±0.13, P < 0.05). The protein expression of IL-8 in group Ⅳ was lower than that in group Ⅰ (CaSki cells: 126±29 vs. 411±112, P < 0.05; pcDNA3.1-IL-8-SiHa cells: 134±47 vs. 327±69, P < 0.05). Apoptotic index in group Ⅳ was higher than that in group Ⅰ (CaSki cells: 81.8±3.0 vs. 26.0±5.6, P < 0.05; pcDNA3.1-IL-8-SiHa cells: 84.4±3.6 vs. 32.0±4.9, P < 0.05). Conclusion Anti IL-8 antibody can inhibit cell migration of human cervical cancer in vitro, inhibit growth and metastasis of transplantation tumor in vivo, and promote apoptosis and necrosis with a dose-dependent way in vivo. Key words: Uterine cervical neoplasms; Interleukin-8; Antibodies, monoclonal