التفاصيل البيبلوغرافية
| العنوان: |
CISD2 enhances the chemosensitivity of gastric cancer through the enhancement of 5- FU-induced apoptosis and the inhibition of autophagy by AKT/ mTOR pathway. |
| المؤلفون: |
Sun, Yi, Jiang, Yingming, Huang, Jintuan, Chen, Hao, Liao, Yi, Yang, Zuli |
| المصدر: |
Cancer Medicine; Oct2017, Vol. 6 Issue 10, p2331-2346, 16p |
| مصطلحات موضوعية: |
GASTRIC mucosa, GASTROINTESTINAL tumors, MTOR inhibitors, APOPTOSIS, REVERSE transcriptase polymerase chain reaction, DIAGNOSIS, CANCER |
| مستخلص: |
Gastric cancer ( GC) is a prevalent upper gastrointestinal tumor characterized by high morbidity and mortality due to imperfect screening systems and the rapid development of resistance to 5-fluorouracil (5- FU). CDGSH iron sulfur domain 2 ( CISD2) has been recently regarded as a candidate oncogene in several types of tumors. It is, therefore, necessary to investigate its biological function and clinical significance in gastric cancer. In this study, the down-regulated expression level of CISD2 in GC compared with adjacent normal tissues was evaluated by quantitative RT- PCR and Western blotting. An immunohistochemical analysis indicated that CISD2 expression in GC was significantly correlated with age ( P = 0.002), Lauren's classification ( P = 0.001), and differentiation ( P = 0.049). Two cell lines, MKN1 and BGC823, were used to analyze the role of CISD2 in gastric carcinogenesis and response to 5- FU through CCK-8 assays, the RT- CES system, Transwell assays, flow cytometry, and confocal fluorescence microscopy. The overexpression of CISD2 resulted in reduced cellular growth and proliferation, inhibition of metastatic ability, and increased apoptosis. 5- FU treatment increased endogenous as well as exogenous overexpression of CISD2 in GC cells. Further investigation revealed that CISD2 enhanced sensitivity to 5- FU via an increase in apoptosis and inhibition of protective autophagy through the activation of the AKT/m TOR pathway. In conclusion, CISD2 is down-regulated in gastric cancer, and its effects on the inhibition of cellular proliferation, metastatic ability, and increased chemotherapy sensitivity are mediated by antagonism to 5- FU-induced autophagy through the AKT/m TOR pathway. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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