Kolorektal Kanser Hücrelerinde Çinko Borat Aracılı Lipid Damlacıkları Azalması ve mTOR İnhibisyonu ile Klonojenik Sağkalımın Kooperatif Baskılanması

Öz

Kolorektal kanser (CRC), dünya çapında kanserle ilişkili ölümlerin önde gelen nedenlerinden biridir ve ilerlemesi ile metastazı, lipid depolanması ve kullanımı dahil olmak üzere metabolik adaptasyonlarla yakından ilişkilidir. Bor türevlerinin hayvanlar ve insanlarda lipid metabolizmasını etkilediği gösterilmiştir. Örneğin, oral borik asit, yağ dokusu ve iskelet kasında termojenik proteinlerin indüklenmesi yoluyla lipolizi artırarak farelerde vücut ağırlığını azaltır. Bu çalışmada, lipid depolanmasını modüle ederek CRC hücre hatları SW480 (primer) ve SW620 (metastatik) üzerindeki çinko boratın (ZnB) potansiyel antikanser etkisini araştırdık. ZnB, hücre canlılığını doza bağımlı olarak azalttı ve SW620 hücreleri daha yüksek direnç gösterdi. Floresan görüntüleme, lipid damlacığı (LD) içeren hücre sayısında azalma olduğunu gösterdi ve bu durum hücresel lipid düzenlenmesinde bir değişiklikle uyumludur. Koloni oluşumu ve yara iyileşme testleri, proliferasyon ve göç yeteneklerinde azalma gösterdi; bu etkiler otofaji indükleyicisi AZD-8055 ile daha da belirginleşti. Lipid depolanmasını ve agresifliği artırdığı bilinen glutamin yoksunluğu koşullarında, ZnB ve AZD-8055’in birlikte uygulanması LD içeriğini, proliferasyonu ve göç kapasitesini belirgin şekilde azalttı. Bu sonuçlar, ZnB’nin CRC hücre sağkalımında rol oynayan lipid homeostazını bozduğunu düşündürmektedir. Bulgularımız, metabolik olarak uyum sağlayabilen ve agresif CRC için lipid metabolizması ve otofajinin birlikte hedeflenmesinin potansiyel terapötik değerine işaret etmektedir.

Anahtar Kelimeler

• Çinko-Borat
• Kolorektal Kanser
• Lipid Metabolizması
• Otofaji
• Proliferasyon

Destekleyen Kurum

TÜBİTAK

Proje Numarası

1919B012419083

Etik Beyan

Bu çalışma yalnızca insan kolorektal kanser hücre hatları (SW480 ve SW620) kullanmıştır. İnsan katılımcılar veya deney hayvanları ile herhangi bir çalışma yapılmamıştır. Tüm işlemler, hücre kültürü ve biyogüvenlik için geçerli kurumsal kılavuzlara uygun olarak gerçekleştirilmiştir.

Zinc Borate–Mediated Reduction of Lipid Droplets and Cooperative Suppression of Clonogenic Survival with mTOR Inhibition in Colorectal Cancer Cells

Öz

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, with progression and metastasis closely tied to metabolic adaptations, including lipid storage and utilization. Boron derivatives have been shown to influence lipid metabolism in animals and humans. Oral boric acid, for example, reduces body weight in mice by inducing thermogenic proteins in adipose and skeletal muscle, promoting lipolysis. In this study, the anticancer potential of zinc borate (ZnB) in CRC cell lines SW480 (primary) and SW620 (metastatic) by modulating lipid storage investigated. ZnB reduced cell viability in a dose-dependent manner, with SW620 cells showing greater resistance. Fluorescence imaging indicated decreased lipid droplet (LD)- containing cells, consistent with possible lipophagy involvement. Colony formation and wound healing assays revealed impaired proliferation and migration, further diminished by the autophagy inducer AZD-8055. Under glutamine-deprived conditions-known to enhance lipid storage and aggressiveness-combined ZnB and AZD-8055 treatment markedly reduced LD content, proliferation and motility. These results suggest that ZnB disrupts lipid homeostasis involved in CRC cell survival. Our findings highlight the potential therapeutic value of co-targeting lipid metabolism and autophagy to combat metabolically adaptive and aggressive CRC.

Anahtar Kelimeler

• Colorectal Cancer
• Lipid Metabolism
• Proliferation
• Autophagy
• Zinc Borate

Destekleyen Kurum

TÜBİTAK

Proje Numarası

1919B012419083

Etik Beyan

This study exclusively utilized established human colorectal cancer cell lines (SW480 and SW620). No experiments involving human participants or animals were conducted. All procedures were performed according to institutional guidelines for cell culture and biosafety.

Kaynakça

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