Sains Malaysiana 53(6)(2024): 1333-1341

http://doi.org/10.17576/jsm-2024-5306-09

 

Dimethyloxalylglycine (DMOG)-Induced Hypoxia Promotes Migratory and Invasive Properties of HCT116 Colon Cancer Cell Line

(Hipoksia Aruhan Dimetiloksalilglisin (DMOG) Menggalakkan Sifat Migrasi dan Invasif Titisan Sel Kanser Kolon HCT116)

 

NOR EZLEEN QISTINA AHMAD1,2, AMIRAH ALHUSNA MOHD YUSOFF1, NUR FARIESHA MD HASHIM1, NURUL AKMARYANTI ABDULLAH1, NORAINA MUHAMAD ZAKUAN1,*

 

1Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

2Institute of Medical Science Technology, Universiti Kuala Lumpur, 43000 Kajang,

Selangor, Malaysia

 

Diserahkan: 1 November 2023/Diterima: 20 Mei 2024

 

Abstract

Hypoxia, a condition characterised by low oxygen levels, leads to increased production of a protein called hypoxia-inducible factor-1 alpha (HIF-1α) in cancer cells. This protein is involved in driving processes such as vascularization, cytoskeletal reorganisation, and epithelial-to-mesenchymal transformation (EMT), which contribute to metastasis. Previous studies used hypoxic workstations, chambers, and incubators to evaluate the effects of hypoxia on colon cancer cell lines. In a cell culture model, hypoxic conditions can also be induced using dimethyloxalylglycine (DMOG) as the hypoxia-mimicking agent. This study aims to investigate the effects of DMOG-induced hypoxia on colon cancer metastasis, focusing on cell migration and invasion. HCT116 cells were subjected to hypoxic conditions by treating them with DMOG, and the expression of HIF-1α proteins was measured at various time points, followed by wound healing and invasion assays. It was found that HIF-1α protein expression increases after 6 h of DMOG induction and persists for 24 h. At 6 and 24 h, a significantly higher percentage of hypoxic cells migrated compared to normoxic cells. The invasion assay demonstrated that hypoxic cells were more invasive than normoxic cells within 24 h. Thus, the increase in migration and invasion of cells is comparable to the increase in HIF-1α expression at 6 and 24 h. These findings suggest that DMOG induces HIF-1α expression in colon cancer cells, leading to enhanced cell migration and invasiveness. The established model can be further utilised in gene knockdown or drug treatment studies to evaluate the effects of hypoxia on cancer cells.

 

Keywords: Colorectal cancer; DMOG; HIF-1α; hypoxia; metastasis

 

Abstrak

Hipoksia, merupakan keadaan yang dicirikan oleh paras oksigen yang rendah, membawa kepada peningkatan pengeluaran protein yang dipanggil hypoxia-inducible factor-1 alpha (HIF-1α) dalam sel kanser. Protein ini terlibat dalam memacu beberapa proses seperti vaskularisasi, penyusunan semula sitoskeleton dan transformasi epitelium-ke-mesenkima (EMT) yang menyumbang kepada metastasis. Kajian terdahulu menggunakan stesen kerja, kebuk dan inkubator hipoksik untuk menilai kesan hipoksia pada titisan sel kanser kolon. Dalam model kultur sel, keadaan hipoksik juga boleh diaruh menggunakan dimetiloksalilglisin (DMOG) sebagai agen memimik hipoksia. Kajian ini bertujuan untuk mengkaji kesan hipoksi yang diaruh DMOG pada metastasis kanser kolon dengan memberi tumpuan kepada migrasi dan invasi sel. Sel HCT116 menjadi hipoksik dengan merawatnya menggunakan DMOG, kemudian ekspresi protein HIF-1α diukur pada pelbagai titik masa, diikuti dengan ujian migrasi dan ujian invasi. Didapati bahawa pengekspresan protein HIF-1α meningkat selepas 6 jam aruhan DMOG dan berterusan selama 24 jam. Pada 6 dan 24 jam, peratusan migrasi sel hipoksik meningkat dengan signifikan berbanding sel normoksik. Ujian pencerobohan menunjukkan bahawa sel hipoksik lebih invasif daripada sel normoksik dalam masa 24 jam. Oleh itu, peningkatan dalam migrasi dan pencerobohan sel adalah selari dengan peningkatan ekspresi HIF-1α pada 6 dan 24 jam. Penemuan ini menunjukkan bahawa DMOG mengaruh pengekspresan HIF-1α dalam sel kanser kolon yang membawa kepada peningkatan kadar migrasi dan pencerobohan sel. Model ini boleh digunakan selanjutnya dalam kajian berkaitan penindasan gen atau rawatan ubat untuk menilai kesan hipoksia pada sel kanser.

 

Kata kunci: DMOG; HIF-1α; hipoksia; kanser kolorektal; metastasis

 

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*Pengarang untuk surat-menyurat; email: noraina@upm.edu.my

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

   

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