Liu Huiyang, Chai Zhirong, Gao Ya, Wang Yanming, Lu Mengmeng
Epigenetics & Translational Medicine Laboratory, School of Life Sciences, Henan University, Kaifeng 475004, China.
The First Affiliated Hospital of Henan University, Henan University, Kaifeng 475004, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Nov 22;57(6):995-1005. doi: 10.3724/abbs.2024210.
Esophageal squamous cell carcinoma (ESCC) is one of the most common forms of malignancy worldwide. However, there is currently a lack of effective chemotherapeutic drugs for ESCC. Ivermectin is a broad-spectrum antiparasitic drug with notable antitumor activity. However, the cellular and molecular mechanisms by which ivermectin inhibits cancer growth remain unclear. In this study, we elucidate the role of ivermectin in ESCC suppression by activating the endoplasmic reticulum (ER) stress and autophagy pathways. In transcriptome analyses, we find that activating transcription factor 4 (ATF4) and DNA damage inducible transcript 3 (DDIT3) are involved in the activation of ER stress by ivermectin. Moreover, ivermectin treatment suppresses the growth of ESCC xenograft tumors in nude mice. Taken together, our results establish the antitumor molecular role of ivermectin in targeting the ER stress-autophagy pathway and suggest that ivermectin is a potential drug candidate for the treatment of ESCC.
食管鳞状细胞癌（ESCC）是全球最常见的恶性肿瘤形式之一。然而，目前针对ESCC缺乏有效的化疗药物。伊维菌素是一种具有显著抗肿瘤活性的广谱抗寄生虫药物。然而，伊维菌素抑制癌症生长的细胞和分子机制仍不清楚。在本研究中，我们通过激活内质网（ER）应激和自噬途径阐明了伊维菌素在ESCC抑制中的作用。在转录组分析中，我们发现激活转录因子4（ATF4）和DNA损伤诱导转录物3（DDIT3）参与了伊维菌素对ER应激的激活。此外，伊维菌素治疗可抑制裸鼠体内ESCC异种移植肿瘤的生长。综上所述，我们的结果确立了伊维菌素在靶向ER应激-自噬途径中的抗肿瘤分子作用，并表明伊维菌素是治疗ESCC的潜在候选药物。
