iPLA2β regulates the dual effects of arachidonic acid in thyroid cancer

IF 2.2 3区医学 Q1 OTORHINOLARYNGOLOGY Head and Neck-Journal for the Sciences and Specialties of the Head and Neck Pub Date : 2024-09-18 DOI:10.1002/hed.27937

Yu Zhang PhD, Wei Su MS, Zhou Yang PhD, Dan Zhao BS, Qing Guan MD, Tian Liao PhD, Duanshu Li BS, Baijie Feng MS, Yunjun Wang MD, Yu Wang MD, Jun Xiang MD

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Abstract

Background

Abnormal arachidonic acid metabolism in the tumor microenvironment is closely related to cancer progression; however, thyroid cancer was rarely researched.

Methods

Through lipidomic analysis, we disclosed that dysregulated arachidonic acid metabolism plays dual effects on thyroid cancer. The promoting role of arachidonic acid in the progression of thyroid cancer cells was evaluated utilizing cell viability (CCK-8 assay) and transwell invasion assays, confirmed by corresponding inhibitors. Lipid peroxidation and the use of various cell death inhibitors confirmed that arachidonic acid confers vulnerability to ferroptosis in thyroid cancer. The roles of arachidonic acid and ferroptosis inducer in thyroid cancer were assessed in a xenograft mouse model.

Results

On one hand, arachidonic acid promotes the progression of thyroid cancer through the cyclooxygenase/prostaglandin pathway; on another hand, arachidonic acid confers vulnerability to ferroptosis through lipoxygenases. Moreover, iPLA2β drives converse roles of arachidonic acid between cancer-progression and ferroptosis vulnerability through releasing free arachidonic acid from the cell membrane. Finally, we confirmed high arachidonic acid diet promotes the development of thyroid cancer in vivo, whereas ferroptosis inducer sulfasalazine dramatically reduced tumor growth of mice with feeding arachidonic acid.

Conclusions

Our research demonstrated the roles of iPLA2β in conversing dual effects of arachidonic acid in thyroid cancer and provides ferroptosis inducer as a potential therapeutic strategy.

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iPLA2β调节花生四烯酸在甲状腺癌中的双重作用

方法通过脂质体分析，我们发现花生四烯酸代谢失调对甲状腺癌具有双重影响。花生四烯酸对甲状腺癌细胞进展的促进作用通过细胞活力（CCK-8 检测）和经孔侵袭检测进行了评估，并通过相应的抑制剂进行了证实。脂质过氧化和各种细胞死亡抑制剂的使用证实花生四烯酸使甲状腺癌细胞易受铁变态反应的影响。结果一方面，花生四烯酸通过环氧化酶/前列腺素途径促进甲状腺癌的进展；另一方面，花生四烯酸通过脂氧合酶使甲状腺癌易受铁氧化作用的影响。此外，iPLA2β通过释放细胞膜上的游离花生四烯酸，促使花生四烯酸在癌症进展和铁变态反应脆弱性之间发挥相反的作用。最后，我们证实了高花生四烯酸饮食会促进体内甲状腺癌的发展，而铁蛋白沉积诱导剂磺胺沙拉嗪能显著减少喂食花生四烯酸的小鼠的肿瘤生长。

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来源期刊

Head and Neck-Journal for the Sciences and Specialties of the Head and Neck 医学-耳鼻喉科学

CiteScore

7.00

自引率

6.90%

发文量

278

审稿时长

1.6 months

期刊介绍： Head & Neck is an international multidisciplinary publication of original contributions concerning the diagnosis and management of diseases of the head and neck. This area involves the overlapping interests and expertise of several surgical and medical specialties, including general surgery, neurosurgery, otolaryngology, plastic surgery, oral surgery, dermatology, ophthalmology, pathology, radiotherapy, medical oncology, and the corresponding basic sciences.