Effects of the Notch1 signaling pathway on human lung cancer A549 cells
Purpose: To evaluate the effects of the Notch1 signaling pathway on human lung cancer A549 cells. Materials and Methods: A549 cells were transfected with recombinant plasmids. Cell proliferation was detected by MTT assay. A tumor-bearing mouse model was established for intratumoral gene injection. A...
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Published in | Experimental lung research Vol. 43; no. 4-5; pp. 208 - 216 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Taylor & Francis
28.05.2017
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Subjects | |
Online Access | Get full text |
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Summary: | Purpose: To evaluate the effects of the Notch1 signaling pathway on human lung cancer A549 cells. Materials and Methods: A549 cells were transfected with recombinant plasmids. Cell proliferation was detected by MTT assay. A tumor-bearing mouse model was established for intratumoral gene injection. Apoptosis-related factors were detected by immunohistochemical assay. Caspase-8, caspase-3, caspase-9, PI3K, pAkt and pSTAT3 expressions were detected by Western blotting. Results: Compared with A549-GFP and A549 cells, A549-ICN cell growth in mice decelerated, tumor volume significantly reduced (p < 0.01), and survival time significantly increased (p < 0.05). Cyclin E and phosphorylated Rb protein expressions were significantly down-regulated. Compared with control, apoptosis-related protein Bcl-2 expression in tumors injected with Notch1 gene was significantly inhibited. After Deltex1 transfection, A549 cell proliferation decelerated, growth was significantly inhibited (p < 0.05), and survival time was significantly extended (p < 0.05). Cyclin E and mutant p53 protein expressions in tumors were down-regulated, phosphorylated Rb expression was almost completely inhibited, and Bcl-2 expression was significantly inhibited. TNF-α-related apoptosis-inducing ligand (TRAIL) inhibited A549-ICN cell growth time- and dose-dependently. After treatment for 24 h or longer, TRAIL induced apoptosis of more A549-ICN cells. Cleaved caspase-3 and cleaved caspase-9 were detected only in A549-ICN cells after 6 h of 40 ng/mL TRAIL treatment, but cleaved caspase-8 was not detected. Combining Notch1 signal with TRAIL inhibited PI3K, phosphorylated Akt and phosphorylated STAT3 expressions. Conclusion: The Notch1 signaling pathway may inhibit A549 cell growth in vitro and in vivo by regulating cell cycle-related and anti-apoptotic protein expressions. Notch1 activation also suppressed A549 cell apoptosis by inhibiting the PI3K/pAkt pathway and activating the caspase-3 pathway in cooperation with TRAIL. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0190-2148 1521-0499 |
DOI: | 10.1080/01902148.2017.1341008 |