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EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
EP1.03-16 - Lysimachia Capillipes Capilliposide C Restores Radiation Sensitivity in Radiation Resistant Lung Cancer Cells by Enhancing ERRFI1 Expression (ID 810)
08:00 - 18:00 | Presenting Author(s): Kan Wu
Radiation therapy is used as the primary treatment for lung cancer. Unfortunately, radiation resistance and local failure remain to be the major clinic problems for lung cancer patients. It is therefore crucial to find new therapeutic targets and/or drugs to enhance the effects of radiation without increasing the adverse effects. Lysimachia capillipes capilliposide C (LC-C) extracts from LC Hemsl. show anti-cancer effects both in vitro and in vivo. The purpose of this study is to investigate a potential therapeutic impact of LC-C as a radiation sensitizer in lung cancer cells.Method
Non small cell lung cancer (NSCLC) cell line A549 was initially irradiated with a total dose of 60 Gy (3 Gy/Fx, 20 Fx, 2-3 Fx/week) to generate radiation-resistant cancer cell line A549-IR. RNA-seq analysis was used to examine the whole-transcriptome alteration in A549-IR cells treated with or without LC-C, and the differentially expressed genes with most significance were verified by RT-qPCR. Colony formation assays were performed to determine the effect of the target gene ErbB receptor feedback inhibitor 1 ( ERRFI1) on radiosensitivity of A549-IR cells. In addition, effects of ERRFI1 on cell cycle distribution, DNA damage repair activity were assessed by flow cytometry and γ-H2AX immunofluorescence staining respectively. Western blot was performed to identify the activation of related signaling pathways. Tumor xenograft experiments were conducted to observe the effect of LC-C and ERRFI1 on radiosensitivity of A549-IR cells in vivo.Result
ERRFI1 was significantly up-regulated in A549-IR cells when cells were treated with LC-C (IC20=3.5 μM). With irradiation treatment, clonogenic formation decreased in the ERRFI1 overexpressed cells when comparing to the parental cells, with reduced survival fraction-2 value from 0.54±0.07 to 0.24±0.06 (p<0.01). The sensitizing enhancement ratio for LC-C was 1.667. Furthermore, ERRFI1 overexpression may enhance radiosensitivity of A549-IR cells in vitro by inducing G2/M phase arrest and inhibiting DNA damage repair. Overexpression of the ERRF11 decreased the activation of EGFR and STAT3 signaling pathways in A549-IR cells. Knocking down ERRFI1 expression in A549-IR cells attenuated the radiosensitization effect of LC-C. Moreover, in a A549-IR cells-derived xenograft model, combination treatment with LC-C (25 mg·kg−1·d−1, qod, ig) and irradiation (6Gy) dramatically enhanced tumor growth suppression comparing with LC-C or radiation alone.Conclusion
LC-C can restore the cells' sensitivity to irradiation through regulation of ERRFI1 expression in lung cancer cells. Combination treatment of LC-C and irradiation may serve as a promising therapeutic strategy to overcome the radiation resistance and ERRFI1 may be a poteintal therapeutic target to improve radiosensitivity in NSCLCs.
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