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OPA3 overexpression modulates lipid droplet production and sensitizes colorectal cancer cells to bevacizumab treatment

HONGBIAO WU*, DONGFANG LIU

Department of Colorectal and Anal Surgery, Ningbo First Hospital, Ningbo, 315010, China

* Corresponding Author: HONGBIAO WU. Email: email

(This article belongs to the Special Issue: Intestinal Epithelial Cells in Health and Disease)

BIOCELL 2024, 48(6), 971-980. https://doi.org/10.32604/biocell.2024.049466

Abstract

Background: Colorectal cancer (CRC) represents a substantial risk to public health. Bevacizumab, the first US FDA-approved antiangiogenic drug (AAD) for human CRC treatment, faces resistance in patients. The role of lipid metabolism, particularly through OPA3-regulated lipid droplet production, in overcoming this resistance is under investigation. Methods: The protein expression pattern of OPA3 in CRC primary/normal tissues was evaluated by bioinformatics analysis. OPA3-overexpressed SW-480 and HCT-116 cell lines were established, and bevacizumab resistance and OPA3 effects on cell malignancy were examined. OPA3 protein/mRNA expression and lipid droplet-related genes were measured with Western blot and qRT-PCR. OPA3 subcellular localization was detected using immunofluorescence. Proliferation and apoptosis were assessed via colony formation and flow cytometry. Tube formation assays were conducted to assess the angiogenic potential of human umbilical vein endothelial cells (HUVECs). Lipid analysis was used to measure the phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) levels in CRC cells. Results: Bioinformatics analysis revealed that OPA3 was downregulated in CRC. Overexpression of OPA3 inhibited CRC cell proliferation, stimulated apoptosis, and suppressed the angiogenic ability of HUVECs. OPA3 effectively reversed the resistance of CRC cells to bevacizumab and decreased lipid droplet production in CRC cells. Additionally, OPA3 reversed the bevacizumab-induced lipid droplet production in CRC cells, thereby increasing CRC cell sensitivity to bevacizumab treatment. Conclusion: This study suggests that OPA3 modulates lipid metabolism in CRC cells and reduces resistance to bevacizumab in CRC cells. Therefore, OPA3 may be a potential therapeutic target against the AAD resistance in CRC.

Graphical Abstract

OPA3 overexpression modulates lipid droplet production and sensitizes colorectal cancer cells to bevacizumab treatment

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APA Style
WU, H., LIU, D. (2024). OPA3 overexpression modulates lipid droplet production and sensitizes colorectal cancer cells to bevacizumab treatment. BIOCELL, 48(6), 971-980. https://doi.org/10.32604/biocell.2024.049466
Vancouver Style
WU H, LIU D. OPA3 overexpression modulates lipid droplet production and sensitizes colorectal cancer cells to bevacizumab treatment. BIOCELL . 2024;48(6):971-980 https://doi.org/10.32604/biocell.2024.049466
IEEE Style
H. WU and D. LIU, "OPA3 overexpression modulates lipid droplet production and sensitizes colorectal cancer cells to bevacizumab treatment," BIOCELL , vol. 48, no. 6, pp. 971-980. 2024. https://doi.org/10.32604/biocell.2024.049466



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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