Objective: To investigate the effect of interleukin-6 (IL-6) on the growth of human lung cancer in vivo as well as in vitro.
Methods: To examine the mRNA level of IL-6 receptor (IL-6R) in high-metastatic human lung giant cell carcinoma cell line PG by means of reverse transcription polymerase chain reaction (RT-PCR). To assess the existence of IL-6 receptor complex (including IL-6R and gp130) with the treatment of PG cells by use of recombinant human IL-6 (rhIL-6), recombinant human oncostatin M (rhOSM), and recombinant human leukemia inhibitory factor (rhLIF), respectively. To detect the expression of IL-6 by Northern blotting hybridization and bioactive assay. To identify the effect of IL-6 secreted by PG cells by use of IL-6 and IL-6R antisense oligodeoxynucleotides (ODNs), and specific neutralizing antibody to IL-6. To document the influence of IL-6 on PG cells growth in vivo through the strategy of the transfection of expression vector inserted antisense IL-6 cDNA.
Results: RT-PCR analysis revealed that PG cells expressed IL-6R mRNA. Any one of the recombinant cytokine IL-6, OSM and LIF stimulated the growth of PG cells in vitro in a concentration-dependent manner. These results demonstrated IL-6 receptor complex exist in PG cells. At the same time, PG cells expressed IL-6 mRNA and secreted bioactive IL-6. Both IL-6 antisense ODNs and IL-6R ODNs inhibited PG cells proliferation. Treatment of PG cells with IL-6 antibodies reduced the growth of PG cells in vitro. PG cells transfected with IL-6 antisense expression vector showed a decreased growth in nude mice.
Conclusion: IL-6 functions as an autocrine growth stimulator for PG cells in vivo as well as in vitro.