Inhibition of tumourigenicity of small cell lung cancer cells by suppressing Id3 expression.

Id3 is over-expressed in small cell lung cancer (SCLC). To test whether the tumourigenicity of SCLC cells can be inhibited by suppressing Id3 expression, we transfected siRNA into SCLC cell line GLC-19 and established two sublines (G-Id3-1 and G-Id3-7) which expressed only 30% of the level of Id3 measured in control transfectants. Suppression of Id3 expression in both G-Id3-1 and G-Id3-7 cells produced significant reductions in proliferation rates and in numbers of colonies formed in soft agar assay. When G-Id3-1, G-Id3-7 and the control transfectants were inoculated subcutaneously into 3 groups (8 each) of nude mice, respectively, all (100%) inoculated animals produced tumours. Although there was no difference in tumour incidents amongst the 3 groups, significant reductions were observed in both size and weight of tumours produced by either G-Id3-1 or G-Id3-7 cells. While the final average volume of tumours produced in control group was 1012.1+/-394 mm(3), it was significantly reduced (p<0.001, p<0.01) by 2.1- and 2.9-fold to 475.7+/-167 mm(3) and 354.3+/-218 mm(3) in groups inoculated with G-Id3-1 and G-Id3-7 cells, respectively. Similar differences were also observed in average weight of tumours. Upon induction of apoptosis by cytotoxin camptothecin, the percentages of apoptotic cells in G-Id3-1 and G-Id3-7 were, respectively >2.4-fold higher than that in control. The results in this study suggest that highly expressed Id3 in SCLC cells may be an important therapeutic target for tumour suppression.