Detailed Abstract
[BR Poster Presentation 1 - Basic Research (Basic Research)]
[BR PP 1-3] SLC38A5 Ameliorates Gemcitabine Resistance By Regulating Ferroptosis In Pancreatic Cancer
Myeong Jin KIM2 , Hyeon Woong KANG2 , Da Eun LEE2 , Woosol Chris HONG2 , Ju Hyun KIM2 , Minsoo KIM2 , Hyo Jung KIM1 , Hyung Sun KIM1 , Joon Seong PARK*1
1 Department Of Surgery, Gangnam Severance Hospital, Yonsei University College Of Medicine, REPUBLIC OF KOREA
2 Brain Korea 21 PLUS Project For Medical Science, Yonsei University, REPUBLIC OF KOREA
Background : Pancreatic cancer has the fourth lowest survival rate in worldwide because it is difficult to detect it in the early stage. Gemcitabine is mainly utilized as a primary treatment to cure the disease. However, it has been proved that gemcitabine has a poor outcome to cure due to its chemoresistance. Therefore, it is necessary to discover a new therapeutic target to overcome the gemcitabine resistance.
Methods : Here, we found that SLC38A5 is highly overexpressed in gemcitabine-resistant pancreatic patients than normal cancer patients. In this study, we found that inhibition of SLC38A5 attenuated gemcitabine resistance in vitro and in vivo. Blockade of SLC38A5 significantly lowered cell proliferation as confirmed by WST assay and glutamine uptake via glutamine assay kit. In addition, inhibition of SLC38A5 induces ferroptosis by inducing lipid ROS through GSH-mediated GPX4 expression and mTOR-SREBP1 signaling.
Results : Here, we found that SLC38A5 is highly overexpressed in gemcitabine-resistant pancreatic patients than normal cancer patients. In this study, we found that inhibition of SLC38A5 attenuated gemcitabine resistance in vitro and in vivo. Blockade of SLC38A5 significantly lowered cell proliferation as confirmed by WST assay and glutamine uptake via glutamine assay kit. In addition, inhibition of SLC38A5 induces ferroptosis by inducing lipid ROS through GSH-mediated GPX4 expression and mTOR-SREBP1 signaling.
Conclusions : Altogether, our results demonstrate that SLC38A5 could be a novel therapeutic target to overcome gemcitabine resistance for PDAC therapy.
Methods : Here, we found that SLC38A5 is highly overexpressed in gemcitabine-resistant pancreatic patients than normal cancer patients. In this study, we found that inhibition of SLC38A5 attenuated gemcitabine resistance in vitro and in vivo. Blockade of SLC38A5 significantly lowered cell proliferation as confirmed by WST assay and glutamine uptake via glutamine assay kit. In addition, inhibition of SLC38A5 induces ferroptosis by inducing lipid ROS through GSH-mediated GPX4 expression and mTOR-SREBP1 signaling.
Results : Here, we found that SLC38A5 is highly overexpressed in gemcitabine-resistant pancreatic patients than normal cancer patients. In this study, we found that inhibition of SLC38A5 attenuated gemcitabine resistance in vitro and in vivo. Blockade of SLC38A5 significantly lowered cell proliferation as confirmed by WST assay and glutamine uptake via glutamine assay kit. In addition, inhibition of SLC38A5 induces ferroptosis by inducing lipid ROS through GSH-mediated GPX4 expression and mTOR-SREBP1 signaling.
Conclusions : Altogether, our results demonstrate that SLC38A5 could be a novel therapeutic target to overcome gemcitabine resistance for PDAC therapy.
SESSION
BR Poster Presentation 1
Poster Presentation 3/24/2023 2:50 PM - 3:50 PM