Encorafenib enhances TRAIL-induced apoptosis of colorectal cancer cells dependent on p53/PUMA signaling
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ORIGINAL ARTICLE
Encorafenib enhances TRAIL-induced apoptosis of colorectal cancer cells dependent on p53/PUMA signaling Zhenqing Sun . Zhigang Qiu . Bin Ma . Zhengkun Wang
Received: 25 August 2020 / Accepted: 6 November 2020 Ó Springer Nature B.V. 2020
Abstract TRAIL has been demonstrated to play a critical role in the apoptosis of colorectal cancer (CRC) cells, but drug resistance markedly restricts its therapeutic effects. Objectives: This study aims to investigate whether encorafenib can enhance TRAILinduced apoptosis of colorectal cancer cells and the underlying mechanism. TRAIL was first used to induce CRC cells. CCK-8 assays were conducted for detecting cell viability of TRAIL-induced CRC cells with encorafenib treatment. Flow cytometry was used to detect the cell apoptosis of CRC cells and western blot was used to measure the expressions of apoptosisrelated proteins. The expressions of DR4, DR5, p53, and PUMA were then evaluated by qPCR and western blot. After transfecting the interference plasmid of p53 into CRC cells, the expressions of PUMA and DR5 were further explored. TRAIL reduced the cell viability of CRC cells, and the inhibition was further reinforced under co-treatment of TRAIL and
encorafenib. Encorafenib also triggered the promotion of CRC cell apoptosis induced by TRAIL. It was also found that encorafenib exerted its promoting effects on cell apoptosis of CRC cells via the elevation of DR5. Besides, encorafenib administration promoted the expression levels of p53 and PUMA in TRAILinduced CRC cells. Furthermore, p53 knockdown attenuated the expression of PUMA and DR5 in TRAIL-induced CRC cells treated with encorafenib. This study indicates that encorafenib stimulates TRAIL-induced apoptosis of CRC cells dependent on p53/PUMA signaling, which may provide instructions for the treatment of CRC. Keywords Encorafenib TRAIL Colorectal cancer p53/PUMA
Introduction Zhenqing Sun and Zhigang Qiu contributed equally to the study. Z. Sun Z. Qiu Z. Wang (&) Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, N0.59, Haier Road, Laoshan District, Qingdao 266100, Shandong, China e-mail: [email protected] B. Ma Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong, China
With an approximate number of 700,000 death cases annually, colorectal cancer (CRC) has become the fourth leading cause of tumor-related death worldwide (Guo et al. 2020). The incidence of CRC is gradually increasing with the growing trend of a western lifestyle among people. In spite of the encouraging news that less invasive technologies have become the substitute for the highly invasive colonoscopy, the average survival time for people with advanced CRC is still short. Thus, there is an urgent need for the new
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Cytotechnology
treatment options for patients with CRC (Roviello et al. 2020). Encorafenib (BraftoviTM) has been confirmed clinically as a BRAF inhibitor due to its inhibitory effect on the activity of BRAF V600E kin
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