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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引用次数: 0
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.
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.