Abstract 3779: Evaluation of efficacy of an RNA aptamer toward non-small cell lung cancer
2016
A specific RNA aptamer (RA16) targeting non-small cell lung cancer (HCI-H460 cells) was previously selected by in vivo SELEX. In this study, we report subsequent studies that determined the effect of RA16 on HCI-H460 cell proliferation in vitro and xenogfrat tumor growth in vivo. Firstly, RA16 apatmer, but SCAP control, was capable of inhibiting cell proliferation in a dose-dependent manner. At 300 nM, RA16 apatmer suppressed cell proliferation by 80%. The IC50 for RA16 was determined at 116.7 nM. Intriguingly, RA16 exhibited no inhibitory effect on HeLa cells even at 600 nM. Moreover, inhibition of HCI-H460 cell growth by RA16 was also observed when it was non-covalently conjugated to Epirubicin(EPI)at the ratio of 1:8 (RA16:EPI). Cell inhibition of 93.6±1.48% was observed with RA16:EPI conjugate (0.375μM:3μM), whereas cell inhibition of 89.0±1.67% and 74.8±5.01% was observed with EPI at 3μM and RA16 alone at 0.375μM, respectively. No inhibition of cell proliferation was observed for the control group treated with cell culture medium. Secondly, an in vivo study was performed to investigate the inhibition of RA16 on HCI-H460 xenograft tumors in mice. Twelve mice with tumor sizes ranging from 50 to 100 mm3 were randomly divided into 2 groups (n = 6). The mice from each group were administrated via intravenous injections of saline (control) or 2 nM of RA16 on days 0, 3, 5, 7, and 9, respectively. Tumor sizes were measured every other day and tumor volumes were calculated by the formula V (mm3) = 1/2×a×b2. The average inhibition rate for mouse tumors of treated group was 54.26±5.87% on day 16 compared with the control group mice. Finally, an in vivo study was performed to evaluate the inhibition of RA16:EPI conjugates on xenograft tumors in mice. Thirty tumor-bearing mice (with tumor sizes about 200∼300 mm3) were randomly divided into 6 groups(n = 5)and treated with various combinations of RA16 and EPI weekly for 3 times. A strong inhibition (64.38±6.45%) of tumor growth was observed when the mice were treated with RA16:EPI conjugate with PEG (EPI at 1.5 mg/kg/week). A moderate inhibition (47.13±10.21%) was observed in mice treated with EPI alone at 1.5 mg/kg/week. Similarly, a moderate inhibition (39.07±5.65%) of tumor growth was observed in mice treated with RA16-EPI conjugate (EPI at 0.5 mg/kg/week) whereas a weak inhibition (28.76±5.65%) was noticed in mouse group treated with EPI alone at 0.5 mg/kg/week. Furthermore, RA16:EPI conjugate (EPI at 1.5 mg/kg/week) inhibited tumor growth by 32.80±6.99% where no PEG was linked to RA16, suggesting that PEGlyation prolongs the efficiency of RA16 in tumor inhibition in vivo. No any inhibition was observed with saline-treated mice. In conclusion, our studies demonstrate that RNA aptamer RA16 specifically inhibits proliferation of transformed HCI-H460 cells in vitro and xenograft tumor growth in vivo and that RA16 conjugated with EPI exhibits enhanced activities both in vitro and in vivo. Citation Format: Hanlu Wang, Haiping Yang, Xinxin Ding, Wei Dai, Yongping Jiang. Evaluation of efficacy of an RNA aptamer toward non-small cell lung cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3779.
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