The role of autophagy induced by pemetrexed in lung adenocarcinoma cells

Park,Ji-Hye; Lee,Young-Rae; So,Hong-Seob; Lee,Kang-Kyoo; Lee,Sam‑Youn; Moon,Sun-Rock; Jo,Hyang-Jeong; Lee,Seoul; Jeong,Kyuyong; Kwon,Kang-Beom; Yang,Sei-Hoon

doi:10.3892/or.2014.3071

The role of autophagy induced by pemetrexed in lung adenocarcinoma cells

Authors:
- Ji-Hye Park
- Young-Rae Lee
- Hong-Seob So
- Kang-Kyoo Lee
- Sam‑Youn Lee
- Sun-Rock Moon
- Hyang-Jeong Jo
- Seoul Lee
- Kyuyong Jeong
- Kang-Beom Kwon
- Sei-Hoon Yang
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Affiliations: Department of Internal Medicine, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea, Department of Oral Biochemistry and Institute of Biomaterials Implant, School of Dentistry, Wonkwang University, Iksan 570-749, Republic of Korea, Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea, Department of Radiation Oncology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea, Department of Thoracic and Cardiovascular Surgery, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea, Department of Pathology, Gunsan Wonkwang University Hospital, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea, Department of Pharmacology, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea
Published online on: March 10, 2014 https://doi.org/10.3892/or.2014.3071
Pages: 2365-2370

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Abstract

Autophagy is known as an important regulatory mediator for cell survival or death and its important role in cancer. Pemetrexed (PTX) has been used in chemotherapy for lung cancer. However, the underlying molecular mechanisms have not been fully clarified. To investigate the role of autophagy induced by PTX in A549 cells, we performed MTT assay, acridine orange staining, western blotting, Annexin V/PI by using the 3-MA autophagy inhibitor. PTX induced autophagy after 48 h treatment in A549 cells. Furthermore, PTX showed acidic vesicular organelles (AVOs) and expressed LC3-II in A549 cells. The induction of autophagy by PTX was inhibited by 3-MA which was confirmed by reduced AVOs. When the autophagy was inhibited, Annexin V was increased. In addition, PARP cleavage was increased as shown by western blotting. Taken together, PTX induced autophagy in A549 cells and these cellular events possibly cause the apoptotic and/or necrotic cell death of A549 cells.

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