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Journal Thoracic Oncology

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Abstracts <strong>Journal</strong> of <strong>Thoracic</strong> <strong>Oncology</strong> • Volume 12 Issue S1 January 2017<br />

Keywords: prognostic prediction, NSCLC, chemotherapy, metabolomics<br />

PUB147 KRAS MUTANTS REGULATED PD-L1 EXPRESSION THROUGH<br />

NF-ƘB AND HIF-1Α PATHWAYS IN NON-SMALL CELL LUNG CANCER<br />

CELLS<br />

Rong Guo, Jie Wang, Hua Bai<br />

Cancer Hospital Chinese Academy of Medical Sciences, Beijing/China<br />

Background: KRAS is one key driving gene for tumorigenesis of lung cancer<br />

and plays an important role in EGFR-TKIs resistance. To investigate the<br />

molecular mechanism of the expression regulation of PD-L1 by mutant KRAS<br />

gene in NSCLC cells, we had pursued researches as described below. Methods:<br />

The expression of PD-L1 and downstream signaling molecules of KRAS gene,<br />

including p-AKT, p-ERK, p-IƘB and HIF-1α, in 13 NSCLC cells were examined by<br />

Western blot. Additionally, two NSCLC cells, H292 and H661, were transfected<br />

with various KRAS mutants and treated with MEK/ERK inhibitor U0126, PI3K/<br />

AKT inhibitor LY294002, and NF-ƘB inhibitor BAY117082, respectively, and<br />

further examination of the expression of PD-L1 and key signaling molecules<br />

of KRAS pathway by Western blot was carried out. Results: The significantly<br />

positive correlation between expression levels of PD-L1 protein and p-IƘB as<br />

well as HIF-1α proteins in 13 NSCLC cells. Furthermore, MEK/ERK and PI3K/<br />

AKT/mTOR all participated in the process of up-regulated PD-L1 expression by<br />

KRAS mutants in both H292 and H661 cells. Notably, the variation tendency of<br />

p-IƘB expression and especially HIF-1α showed strong consistency with PD-L1<br />

in both H292 and H661 cells treated with KRAS mutants and the three kinds<br />

of inhibitor.Conclusion: Our findings revealed that KRAS mutants regulated<br />

PD-L1 expression through NF-ƘB and HIF-1α pathways in NSCLC cells, and<br />

suggested the correlation between EGFR-TKIs resistance and immune<br />

escape as well as significance of combined treatment of target therapy and<br />

immunotherapy in NSCLC.<br />

PUB149 CROTON TIGLIUM EXTRACT INDUCES THE APOPTOSIS IN<br />

HUMAN LUNG CANCER A549 CELLS<br />

Changyou Li, Xiao Wu, Rongli Sun, Peng Zhao, Fengjuan Liu, Chunling Zhang<br />

Qingdao Central Hospital, Qingdao/China<br />

Background: Croton, a large genus of Euphorbiaceae, is widely distributed in<br />

tropical regions of South-East Asia and China. Many researchers previously<br />

reported the pharmacological and physiological actions of Croton species on<br />

anti-inflammatory, anticonvulsant and wound healing properties .Mature<br />

Croton tiglium contains large amounts of natural medical components, in<br />

which croton alkaloid, flavonoids and diterpenes are anticancer agents.<br />

The study on application of Croton in lung cancer is lacking. In this study,<br />

we investigated the regulating effects of Croton tiglium extract on A549<br />

cell proliferation and apoptosis. Methods: Preparation of Croton tiglium<br />

seed extract. A549 human lung cancer cell cultures Cell viability assay Flow<br />

cytometric analysis of apoptosis Results: The MTT assay showed that Croton<br />

tiglium extract could exert a significant inhibitory effect on the proliferation<br />

of A549 cells. (Figure 1, P

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