Abstract 995: Regulation of radiation by autophagic modulator

Abstract

Abstract Introduction: On account of limited therapeutic options for advanced and recurrent cervical cancer, novel therapeutic modalities are being investigated based on translational research. Among the promising topics is autophagy. Autophagy can be refered to as a double edged sword in a way that it is known to play a role in both tumor cell suppression and survival. This study was carried out to determine the effect of autophagy in treatment of cervical cancer cells with radiation alone and with autophagy inducer or inhibitor. Methods: Human cervical cancer cells, Hela and Caski were used. Western blot was implemented to detect protein expression. Fluorescence microscopy and inverted microscopy guided inspection confimed autophagy. Hela and Caski cells were irradiated with r-rays (2 Gy / min) and again each time after treatment with autophagy inducer (Rapamycin) and inhibitor (3-MA). Expression of LC3 and cell deaths in two cell preparations were examined. Results: Notable increment of LC3 expression were detected after radiation in both cell lines by western blot and microscope analyses. Radiation of pre-Rapamycin treated cells showed further increased LC3 expression and pre-3-MA treated cells, less increased LC3 expression than radiation alone compared to non-treated, not radiated cells. Cell viability decreased to 75% in Hela cells and 79% in Caski cells after radiation. When treated with Rapamycin, cell viabilities were 59% and 65%, and with 3-MA, 65% and 70% in each cell lines. Discussion: Radiation induces autophagy in cervical cancer cell lines. Autophagy induced by radiation could be modified when treated with Rapamycin / 3-MA which leads to more cell deaths. Further investigations are needed to identify the specific pathways mediating post-IR induced autophagy in order to confirm the functional link between autophagy and radiation treatment. Inhibition of autophagy seems to promote more cells to undergo apoptosis, however, the relationship between autophagy and apoptosis with IR treatment in cervical cancer cells remain to be enlightened. Induction of autophagy may interfere with the mechanism of homeostasis that is originally preserved by autophagy itself, and leads to cell death possibly altogether with apoptosis. The pathway via which this process conducts also waits to be distinguished. Citation Format: Keun Ho Lee, Yoon Kyung Lee. Regulation of radiation by autophagic modulator. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 995. doi:10.1158/1538-7445.AM2015-995