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TRPV1 inhibition suppresses non-small cell lung cancer progression by inhibiting tumour growth and enhancing the immune response

作者:Wang Yang, Yu Zhang, Jing Ouyang, Hanying Yi, Shiyu Wang, Dongbo Liu, Yingying Dai, Kun Song, Wenwu Pei, Ziyang Hong, Ling Chen, Wei Zhang, Zhaoqian Liu, Howard L. McLeod, Yijing He · 发表于:Cellular Oncology · 年份:2023 · DOI:10.1007/s13402-023-00894-7 · 被引用次数:14 · 研究领域:Ion Channels and Receptors、Cancer, Stress, Anesthesia, and Immune Response、NF-κB Signaling Pathways

TRPV1 is a nonselective Ca 2+ channel protein that is widely expressed and plays an important role during the occurrence and development of many cancers. Activation of TRPV1 channels can affect tumour progression by regulating proliferation, apoptosis and migration. Some studies have also shown that activating TRPV1 can affect tumour progression by modulating tumour immunity. However, the effects of TRPV1 on the development of non-small cell lung cancer (NSCLC) have not been explored clearly. The Cancer Genome Atlas (TCGA) database and spatial transcriptomics datasets from 10 × Genomics were used to analyze TRPV1 expression in various tumour tissues. Cell proliferation and apoptosis were examined by cell counting kit 8 (CCK8), colony formation, and flow cytometry. Immunohistochemistry, qPCR, and western blotting were used to determine the mRNA and protein expression levels of TRPV1 and other related molecules. Tumour xenografts in BALB/C and C57BL/6J mice were used to determine the effects of TRPV1 on NSCLC development in vivo. Neurotransmitter content was examined by LC-MS/MS, ELISA and Immunohistochemistry. Immune cell infiltration was assessed by flow cytometry. In this study, we found that TRPV1 expression was significantly upregulated in NSCLC and that patients with high TRPV1 expression had a poor prognosis. TRPV1 knockdown can significantly inhibit NSCLC proliferation and induce cell apoptosis through Ca 2+ -IGF1R signaling. In addition, TRPV1 knockdown resulted in inc...