Internalization and lethal effect of 131I-RC-160 on A549 lung carcinoma cells transfected with hSSTR2 gene

Objective: Introducing new gene to make an useful expression of the host cell is of clinical potential. In the current study, the internalization of the radioiodinated somatostatin analog 125I-RC- 160 by A549 lung carcinoma cells transfected with human somatostatin receptor subtype 2 (hSSTR2) gene (A549-hSSTR2), and the lethal effect of 131I-RC-160 on A549-hSSTR2 cells were investigated. Methods: A549-hSSTR2 cells expressing hSSTR2 or A549-pc3 cells without hSSTR2 expression were incubated at 37 degree C with 125I-RC-160 for different time(0.25, 0.5, 1,4, 8, 20 and 24 h). The internalization of the radioligand was determined at the end of incubation. By using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the lethal effect of various dosage of 131I-RC-160, Na131I, RC-160 on A549-hSSTR2 and A549-pc3 after 24, 48, 72, 96 h incubation were measured. Results: 125I-RC-160 was rapidly internalized mediated via the membrane receptor of A549-hSSTR2. The binding radioactivity of A549-hSSTR2 cells [(18.2±1.9)% of total amount added] was higher than that of A549-pc3 cells (5.7± 1.4)% after 1 h of incubation (P<0.05). The internalization showed time-dependent manner with concomitant decrease of membrane binding. 131I-RC-160 had stronger growth-inhibit effect on A549-hSSTR2 cells than on A549-pc3 cells. Conclusion: 125I-RC-160 could internalize the A459-hSSTR2 cells with enhanced lethal effect than A549-pc3 control, proving the concept of exogenous receptor gene mediated internal radiation therapy of cancers. (authors)