Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway
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 m...
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2024-11-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024210 |
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| author | Liu Huiyang Chai Zhirong Gao Ya Wang Yanming Lu Mengmeng |
| author_facet | Liu Huiyang Chai Zhirong Gao Ya Wang Yanming Lu Mengmeng |
| author_sort | Liu Huiyang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3304b1ef6deb41eeaf07c1e7c5140975 |
| institution | OA Journals |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-3304b1ef6deb41eeaf07c1e7c51409752025-08-20T02:37:43ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-11-0157995100510.3724/abbs.202421020d259ccIvermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathwayLiu Huiyang0Chai Zhirong1Gao Ya2Wang Yanming3Lu Mengmeng4["Epigenetics & Translational Medicine Laboratory, School of Life Sciences, Henan University, Kaifeng 475004, China"]["Epigenetics & Translational Medicine Laboratory, School of Life Sciences, Henan University, Kaifeng 475004, China"]["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"]["Epigenetics & Translational Medicine Laboratory, School of Life Sciences, Henan University, Kaifeng 475004, China","State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng 475004, China"]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.https://www.sciengine.com/doi/10.3724/abbs.2024210ivermectinESCCER stressATF4autophagy |
| spellingShingle | Liu Huiyang Chai Zhirong Gao Ya Wang Yanming Lu Mengmeng Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway Acta Biochimica et Biophysica Sinica ivermectin ESCC ER stress ATF4 autophagy |
| title | Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway |
| title_full | Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway |
| title_fullStr | Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway |
| title_full_unstemmed | Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway |
| title_short | Ivermectin inhibits the growth of ESCC by activating the ATF4-mediated endoplasmic reticulum stress-autophagy pathway |
| title_sort | ivermectin inhibits the growth of escc by activating the atf4 mediated endoplasmic reticulum stress autophagy pathway |
| topic | ivermectin ESCC ER stress ATF4 autophagy |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024210 |
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