Objective: To study the effects of two cAMP analogs with different site-selectivity on growth and differentiation of metastatic human lung cancer cells.
Methods: The methods used include cell culture, in vitro invasion assay, soft agar colony formation assay, immunocytochemistry and electron microscopy. A metastatic human lung cancer cell line gwas treated with dibutyryl cAMP (db-cAMP, non-site-selective) or 8-chloro-cAMP (8-Cl-cAMP, site-selective for type II PKA).
Results: Treatment of PG cells with 1 mmol/L of db-cAMP for 7 days resulted in 48% growth inhibition, while treatment with 20 mumol/L of 8-Cl-cAMP gave 70% growth inhibition. The growth inhibitory effect of db-cAMP was shown to be reversible, while that of 8-Cl-cAMP was not. The ability of PG cells to penetrate matrigel-coated membrane and to form colonies in soft agar was also significantly inhibited by treatment with these two drugs. Microscopic observation showed that cells formed elongated cytoplasmic processes and increased expression of neuron-specific enolase as well as chromogranin after treatment.
Conclusion: The objective to inhibit malignancy could be reached by activation of specific PKA with site-selective cAMP analogs.