Abstract 4144: A tissue-microfluidic derived aptamer displays prognostic and therapeutic characteristics in serous ovarian carcinoma through heat shock protein 70(HSP70)

Abstract

Abstract Background: Previously, we have identified aptamers through ovarian cancer (OC) tissue microfluidic platform which show high specificity to ovarian cancer tissue and cells. However, the clinical diagnostic and therapeutic roles of these aptamers are still largely unknown. Materials and Methods: Liquid chromatography-mass spectrometry (LC-MS) was used to find binding candidates of aptamer, Tx-01, from serous type ovarian cancer cells. Immunohistochemistry (IHC), clinical survival analysis, western blotting and confocal microscopic images were performed to detect the expression of Tx-01 and HSP70/ Notch1 intracellular domain (NICD) in OC tissues. The functions of Tx-01 were studied in vitro and in vivo experiments. Inhibitors treatment, nuclear protein extraction and western blotting were carried out to demonstrate the possible mechanisms of Tx-01 function. Results: High expression Tx-01 in OC tissues was correlated to poor patients' survival in serous ovarian carcinoma. In vitro experiments showed that Tx-01 has a feature of recognizing membrane-bound HSP70. In the meantime, Tx-01 inhibit HSP70 signal activation via interrupting intracellular HSP70/NICD interaction to reduce cell migration and invasion. Furthermore, Tx-01 inhibited the tumor growth in the mice experiment. Conclusion: Our data showed that Tx-01 acted as a prognostic predictor in serous OC through recognizing the membrane-bound HSP70. Also, Tx-01 reduced the tumor cell migration, invasion through blocking HSP70 signal activation. Thus, our work demonstrated that Tx-01 might be a prognostic biomarker and potential inhibitor in serous OC therapy. Citation Format: Chang-Ni Lin, Yu-Ling Liang, Pei-Ying Wu, Gwo-Bin Vincent Lee, Keng-Fu Hsu. A tissue-microfluidic derived aptamer displays prognostic and therapeutic characteristics in serous ovarian carcinoma through heat shock protein 70(HSP70) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4144.