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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
Received: 1 November
2023/Accepted: 20 May 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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*Corresponding
author; email: noraina@upm.edu.my
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