Abstract 5156: A synthesized RNA aptamer targeting and inhibiting non-small cell lung cancer

Abstract

Abstract A specific RNA aptamer (RA16) targeting non-small cell lung cancer (NCI-H460 cells) was previously reported by in vivo SELEX. The aptamer RA16 was identified specifically targeting and inhibiting human NCI-H460 cell proliferation in vitro, as well as xenograft tumor tissues in vivo. In this study, we synthesized RNA aptamer (syn-RA16) and make comparison studies with transcribed RNA aptamer (trans-RA16) in vitro in respect of the specific targeting and direct inhibitory activity towards NCI-H460 cells.To characterize the targeting specificity in vitro, biotin-labeled syn-RA16 and trans-RA16 were incubated with NCI-H460 cells, other tumor cell lines or normal control cells. Specific fluorescent binding was observed only for NCI-H460 cells, but not for HEK293T, Hela, and Jurkat cells or buffer control. Moreover, binding affinity of Kd values to the NCI-H460 cells for syn-RA16 and trans-RA16 were determined at 24.75±2.28 nM and 12.14±1.46 nM(n=3), respectively, by flow cytometry using streptavidin-PE labelling, indicating that the specific targeting binding affinity for syn-RA16 was highly retained, as trans-RA16. On the other hand, syn-RA16 aptamer, like trans-RA16 aptamer, was also capable of inhibiting non-small cell lung cancer cell (H460) proliferation in a dose-dependent manner. At 300 nM, syn-RA16 aptamer suppressed cell proliferation by 84.5%, comparing by 86.8% with trans-RA16. The IC50 for syn-RA16 was determined at 118.4±1.1 nM, while trans-RA16 was at 105.7±1.2 nM (n=4). Intestinally, both syn-RA16 and trans-RA16 exhibited no any inhibitory effect on HeLa and Jurkat cell lines even at concentration of 600 nM. In conclusion, a specific entire RA16 RNA aptamer was synthesized. The synthesized RA16, like transcribed RA16 aptamer, demonstrated the specific targeting ability and inhibitory activity to human NCI-H460 cells. The syn-RA16 could be potential to develop a diagnostic kit or treatment for NCI-H460 cell-related non-small cell lung cancer in the clinic. Citation Format: Hanlu Wang, Meng Qin, Zhihua Ren, Irvin S.Y. Chen, Yongping Jiang. A synthesized RNA aptamer targeting and inhibiting non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5156. doi:10.1158/1538-7445.AM2017-5156