title: Down-regulation of expression of interleukin-6 and its receptor results in growth inhibition of MCF-7 breast cancer cells.
abstract: Interleukin-6 (IL-6) plays an important role in the neoplastic process through its action on cancer cell adhesion, motility, proliferation, tumor-specific antigen expression, and thrombopoiesis. IL-6 exerts its activity by binding to a high affinity receptor complex consisting of two membrane glycoproteins: the 80 kDa IL-6 a-receptor subunit (IL-6R) and the 130 kDa signal-transducing protein (GP130). In the present study, MCF-7 breast cancer cells were cultured with human IL-6 and IL-6 soluble receptor (sIL-6R). MCF-7 cells were also treated with either antibodies specific to human IL-6 and IL-6R, or synthetic antisense oligodeoxynucleotides (ODNs) targeted to IL-6 and IL-6R genes. Cell growth was measured, and it was found that human IL-6 and sIL-6R did not significantly increase the proliferation of MCF-7 cells. When IL-6 produced by the MCF-7 cells was bound by rabbit anti-human IL-6 antibody, there was a significant dose-dependent inhibition of cell proliferation. IL-6 and IL-6R antisense ODNs caused a marked and specific decrease in IL-6 and IL-6R mRNA and proteins, respectively. Both IL-6 and IL-6R antisense ODNs significantly inhibited the proliferation of MCF-7 cells, but the inhibitory effect of IL-6R antisense ODN was greater than that of IL-6 antisense ODN (IC₅₀: IL-6R: 1 μM; IL-6: 5 μM, 72-hour incubation). Addition of exogenous IL-6 partially reversed the growth inhibition caused by IL-6 antisense ODN but not the growth inhibition caused by IL-6R antisense ODN. In conclusion, IL-6 plays an important role in maintaining the growth of MCF-7 breast cancer cells. These results suggest careful modulation of IL-6 and IL-6R expression of cells as a potential approach for breast cancer therapy.
authors.affiliation: Mastology Research Institute, Elliott-Ellott-Head Breast Cancer Research and Treatment Center, 17050 Medical Center Drive, 4th Floor, Baton Rouge, LA 70816, USA. xjiang@eehbreastca.com
authors.forename: Xian-Peng
authors.initials: XP
authors.lastname: Jiang
authors.forename: Ding Cheng
authors.initials: DC
authors.lastname: Yang
authors.forename: Robert L
authors.initials: RL
authors.lastname: Elliott
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Head
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D015536:Down-Regulation; D004587:Electrophoresis, Agar Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D015850:Interleukin-6; D019947:Receptors, Interleukin-6