دورية أكاديمية
Chronic Microcystin-LR Exposure Induces Hepatocarcinogenesis via Increased Gankyrin in Vitro and in Vivo
| العنوان: | Chronic Microcystin-LR Exposure Induces Hepatocarcinogenesis via Increased Gankyrin in Vitro and in Vivo |
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| المؤلفون: | Lixiong He, Yujing Huang, Qiaonan Guo, Hui Zeng, Chuanfen Zheng, Jia Wang, Ji-an Chen, Lingqiao Wang, Weiqun Shu |
| المصدر: | Cellular Physiology and Biochemistry, Vol 49, Iss 4, Pp 1420-1430 (2018) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Physiology LCC:Biochemistry |
| مصطلحات موضوعية: | Microcystin-LR, Gankyrin, Malignant transformation, Oncogene, Hepatocellular carcinoma, Physiology, QP1-981, Biochemistry, QD415-436 |
| الوصف: | Background/Aims: Our recent study indicated that the serum microcystin-LR (MC-LR) level is positively linked to the risk of human hepatocellular carcinoma (HCC). Gankyrin is over-expressed in cancers and mediates oncogenesis; however, whether MC-LR induces tumor formation and the role of gankyrin in this process is unclear. Methods: We induced malignant transformation of L02 liver cells via 35 passages with exposure to 1, 10, or 100 nM MC-LR. Wound healing, plate and soft agar colony counts, and nude mice tumor formation were used to evaluate the tumorigenic phenotype of MC-LR-treated cells. Silencing gankyrin was used to confirm its function. We established a 35-week MC-LR exposure rat model by twice weekly intraperitoneal injection with 10 μg/kg body weight. In addition, 96 HCC patients were tested for tumor tissue gankyrin expression and serum MC-LR levels. Results: Chronic low-dose MC-LR exposure increased proliferation, mobility, clone and tumor formation abilities of L02 cells as a result of gankyrin activation, while silencing gankyrin inhibited the carcinogenic phenotype of MC-LR-treated cells. MC-LR also induced neoplastic liver lesions in Sprague-Dawley rats due to up-regulated gankyrin. Furthermore, a trend of increased gankyrin was observed in humans exposed to MC-LR. Conclusion: These results suggest that MC-LR induces hepatocarcinogenesis in vitro and in vivo by increasing gankyrin levels, providing new insight into MC-LR carcinogenicity studies. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1015-8987 1421-9778 00049344 |
| Relation: | https://www.karger.com/Article/FullText/493446; https://doaj.org/toc/1015-8987; https://doaj.org/toc/1421-9778 |
| DOI: | 10.1159/000493446 |
| URL الوصول: | https://doaj.org/article/d729a3f70d8741c78e167221d3f9ff04 |
| رقم الأكسشن: | edsdoj.729a3f70d8741c78e167221d3f9ff04 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10158987 14219778 00049344 |
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| DOI: | 10.1159/000493446 |