Oncotarget

Research Papers:

Enhancement of TRAIL-induced apoptosis by 5-fluorouracil requires activating Bax and p53 pathways in TRAIL-resistant lung cancers

Uddin MD. Nazim, Mohammad Rasheduzzaman, You-Jin Lee, Dai-Wu Seol and Sang-Youel Park _

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Oncotarget. 2017; 8:18095-18105. https://doi.org/10.18632/oncotarget.14994

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Abstract

Uddin MD. Nazim1, Mohammad Rasheduzzaman1, You-Jin Lee1, Dai-Wu Seol2, Sang-Youel Park1

1Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea

2Faculty of Pharmacy, Chung-Ang University School of Pharmacy, Seoul 156-756, Republic of Korea

Correspondence to:

Sang-Youel Park, email: sypark@chonbuk.ac.kr

Keywords: 5-fluorouracil, TRAIL, apoptosis, lung cancer cells

Received: August 01, 2016    Accepted: January 03, 2017    Published: February 02, 2017

ABSTRACT

Lung cancer, especially lung adenocarcinoma, is one of the main causes of death worldwide. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a primary anticancer agent and a member of the tumor necrosis factor family that selectively induces apoptosis in various tumor cells, but not in normal cells. Combination chemotherapy can be used for treating specific cancer types even at progressive stages. In the present study, we observed that 5-fluorouracil, which exerts anticancer effects by inhibiting tumor cell proliferation, enhanced TRAIL-induced apoptosis of TRAIL-resistant human adenocarcinoma A549 cells. Interestingly, 5-fluorouracil treatment markedly increased Bax and p53 levels and 5-fluorouracil and TRAIL cotreatment increased Ac-cas3 and Ac-cas8 levels compared with those in control cells. Taken together, the present study demonstrated that 5-fluorouracil enhances TRAIL-induced apoptosis in TRAIL-resistant lung adenocarcinoma cells by activating Bax and p53, and also suggest that TRAIL and 5-fluorouracil cotreatment can be used as an adequate therapeutic strategy for TRAIL-resistant human cancers.


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