| Status | 已發表Published |
| Platycodin D potentiates proliferation inhibition and apoptosis induction upon AKT inhibition via feedback blockade in non-small cell lung cancer cells | |
Li, T; Chen, X; Chen, X. P.; Ma, DL; Leung, C. H.; Lu, J.
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| 2016-09-01 | |
| Source Publication | The International Symposium for Graduate Students on Pharmaceutical Sciences 2016 and the 2nd Annual AAPS-SYSU Student Chapter Research Symposium
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| Abstract | Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide. AKT, as a frequently overexpresses and constitutively active kinase within NSCLC cells, is recognized as a promising target for NSCLC treatment. However, inhibition of AKT relieves the feedback inhibition of upstream receptor tyrosine kinases (RTKs) that may weaken the efficiency of AKT inhibitors. Platycodin D (PD), a saponin isolated from a widely-used traditional Chinese medicine Platycodonis Radix, is now found to remarkably enhance the anti-proliferative effect of AKT inhibitors. In this study, the feedback signals upon AKT inhibition were disclosed and the combinatorial activity of AKT inhibitor MK2206 and PD on cell proliferation, apoptosis and related signaling were detected. Combined treatment of PD and MK2206 led to an amplified anti-proliferative and apoptotic activity in NSCLC cells. Long-term AKT inhibition by MK2206 induced feedback activation with up-regulation of RTKs, including EGFR and HER-2. Co-treatment of MK2206 with PD could abolish this feedback survival by decrease of EGFR, HER-2, and p-AKT, and profound inhibition of 4E-BP1. Similarly, feedback activation in response to reduction of AKT expression by small interfering RNA (siRNA) was also blocked by PD and the apoptotic effect was further enhanced. Thus, PD potentiated the proliferation inhibition and apoptosis induction of both the AKT inhibitor and siRNA of AKT. These findings also reveal the limitations of suppressing the feedback-regulated pathways by monotherapy and establish a mechanistic rationale for a novel combination approach targeting AKT for the treatment of NSCLC. |
| Keyword | NSCLC platycodin D AKT 4E-BP1 combinational therapy |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 36492 |
| Document Type | Conference paper |
| Collection | University of Macau |
| Corresponding Author | Lu, J. |
| Recommended Citation GB/T 7714 | Li, T,Chen, X,Chen, X. P.,et al. Platycodin D potentiates proliferation inhibition and apoptosis induction upon AKT inhibition via feedback blockade in non-small cell lung cancer cells[C], 2016. |
| APA | Li, T., Chen, X., Chen, X. P.., Ma, DL., Leung, C. H.., & Lu, J. (2016). Platycodin D potentiates proliferation inhibition and apoptosis induction upon AKT inhibition via feedback blockade in non-small cell lung cancer cells. The International Symposium for Graduate Students on Pharmaceutical Sciences 2016 and the 2nd Annual AAPS-SYSU Student Chapter Research Symposium. |
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