| Status | 已發表Published |
| Feedback loops blockade by platycodin D potentiates the anticancer potential upon AKT inhibition in non-small cell lung cancer cells | |
Li, T ; Chen, X; Chen, X. P.; Wang, Y. T.; Lu, J. 
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| 2016-10-01 | |
| Source Publication | The 9th Chinese Conference on Oncology & the 15th Cross-Strait Academic Conference on Oncology
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| Abstract | Objective: Non-small cell lung cancer (NSCLC) is the most common cause of cancer death worldwide with poor prognosis and low 5-year survival. 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 feedback inhibition of upstream receptor tyrosine kinases (RTKs), which may attenuate the efficiency of AKT inhibitors. This study aims to investigate the combinatorial activity of AKT inhibitor MK2206 and platycodin D (PD), a saponin isolated from a widely-used traditional Chinese medicine Platycodonis Radix, in cell proliferation, apoptosis and relative signaling on NSCLC cells. Method: MTT assay and colony formation assay were performed to evaluate cell viability and colony formation activity after cotreatment with MK2206 and PD, along with flow cytometry and caspase activity assay for apoptosis. Western blotting was conducted to determine the relative protein levels. Results: Long-term AKT inhibition by MK2206 induces feedback activation with upregulated RTKs, including EGFR and HER-2. Cotreatment of MK2206 with PD could fully abolish this feedback survival by decrease of EGFR, HER-2, p-AKT and profound inhibition of 4E-BP1. Similarly, feedback activation in response to reduction of AKT expression by small interfering RNA (siRNA) is also blocked by PD and apoptotic effect is further enhanced. Conclusion: PD potentiates proliferation inhibition and apoptosis induction of both AKT inhibitor and siRNA. These findings also reveal the limitations of monotherapy for inhibiting feedback-regulated pathways and established 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 | 36495 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Lu, J. |
| Recommended Citation GB/T 7714 | Li, T,Chen, X,Chen, X. P.,et al. Feedback loops blockade by platycodin D potentiates the anticancer potential upon AKT inhibition in non-small cell lung cancer cells[C], 2016. |
| APA | Li, T., Chen, X., Chen, X. P.., Wang, Y. T.., & Lu, J. (2016). Feedback loops blockade by platycodin D potentiates the anticancer potential upon AKT inhibition in non-small cell lung cancer cells. The 9th Chinese Conference on Oncology & the 15th Cross-Strait Academic Conference on Oncology. |
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