Jong, Kelly Xue Jing and Mohamed, Elsa Haniffah Mejia and Syafruddin, Saiful Effendi and Faruqu, Farid Nazer and Vellasamy, Kumutha Malar and Ibrahim, Kamariah and Ibrahim, Zaridatul Aini (2024) IL-8 and PI3K pathway influence the susceptibility of TRAIL-sensitive colorectal cancer cells to TRAIL-induced cell death. Molecular Biology Reports, 51 (1). ISSN 0301-4851, DOI https://doi.org/10.1007/s11033-024-09895-7.
Full text not available from this repository.Abstract
Background Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an apoptosis inducer that exhibits an ideal therapeutic safety profile with less adverse effects than conventional chemotherapy. However, the occurrence of TRAIL resistance has been reported in various cancers including colorectal cancer (CRC). Substantial efforts have been channelled towards managing TRAIL resistance including identifying molecular targets. Interleukins (ILs) have been recently shown to play critical roles in modulating TRAIL sensitivity in cancer cells. Methods and Results This study investigated the roles of two ILs, IL-8 and IL alpha, in TRAIL resistance in CRC. TRAIL-resistant HT-29 and TRAIL-sensitive HCT 116 cells, were treated with human recombinant IL-8 and IL-1 alpha. The results indicated that treatment with IL-8 (2.5 ng/mL) significantly protected TRAIL-sensitive HCT 116 cells from TRAIL-induced cell death (p < 0.05). However, IL-1 alpha did not play a role in modulating CRC cells' responses to TRAIL. Data from RT-qPCR and Western blotting revealed the molecular regulations of IL-8 on TRAIL decoy receptor genes (OPG) and autophagy-related genes (BECN1 and LC3B) expression. The activation of the phosphoinositide 3-kinase (PI3K) pathway was shown to counteract TRAIL-induced cell death. By inhibiting its activation with wortmannin, the protective role of IL-8 against TRAIL treatment was reversed, suggesting the involvement of the PI3K pathway. Conclusion Collectively, findings from this study identified the role of IL-8 and PI3K in modulating CRC cells' sensitivity to TRAIL. Further validation of these two potential molecular targets is warranted to overcome TRAIL resistance in CRC.
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Education, Malaysia [Grant No: FRGS/1/2020/SKK0/UM/02/36 (FP108-2020)], Ministry of Higher Education under the Fundamental Research Grant Scheme (FRGS) [Grant No: PV001-2021], MAKNA Cancer Research Award, Faculty of Medicine Postgraduate Scholarship Scheme (FOMPSS) |
| Uncontrolled Keywords: | TRAIL resistance; IL-8; IL-1 alpha; CRC; PI3K; Autophagy |
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 03 Nov 2025 12:11 |
| Last Modified: | 03 Nov 2025 12:14 |
| URI: | http://eprints.um.edu.my/id/eprint/46331 |
Actions (login required)
 |
View Item |
