ReferenceID 6140
Organic anion transporters and PI3K-AKT-mTOR pathway mediate the synergistic anticancer effect of pemetrexed and rhein
J Cell Physiol
The aim of this study was to explore whether rhein could enhance the effects of pemetrexed (PTX) on the therapy of non-small-cell lung cancer (NSCLC) and to clarify the associated molecular mechanism. Our study shows tha
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Record Fields
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- Reference Id
- 6140
- Evidence Id
- 22730
- Core Evidence Id
- 22730
- Source Reference Id
- 5540
- Herb2 Reference Id
- HBREF006337
- Subject Paper Key
- HBIN042199_31587272
- Pubmed Id
- 31587272
- Doi
- 10.1002/jcp.29218
- Paper Title
- Organic anion transporters and PI3K-AKT-mTOR pathway mediate the synergistic anticancer effect of pemetrexed and rhein
- Paper Abstract
- The aim of this study was to explore whether rhein could enhance the effects of pemetrexed (PTX) on the therapy of non-small-cell lung cancer (NSCLC) and to clarify the associated molecular mechanism. Our study shows that rhein in combination with PTX could obviously increase the systemic exposure of PTX in rats, which would be mediated by the inhibition of organic anion transporters (OATs). Furthermore, the toxicity of PTX was significantly raised by rhein in A549 cells in a concentration-dependent manner. Concomitant administration of rhein and PTX-induced cell apoptosis compared with PTX alone in flow cytometry assays, which was further validated by the protein expressions of the apoptotic markers B-cell lymphoma-2/Bcl-2-associated x (Bcl-2/Bax) and Cleaved-Caspase3 (Cl-Caspase3). Meanwhile, the results of monodansylcadaverine (MDC) dyeing experiments showed that PTX-induced autophagy could be enhanced by combination therapy with rhein in A549 cells. Western blot analysis indicated that the synergistic effect of rhein on PTX-mediated autophagy may be interrelated to PI3K-AKT-mTOR pathway inhibition and to the enhancement of p-AMPK and light chain 3-II (LC3-II) protein levels. From these findings, it could be surmised that rhein enhanced the antitumor activity of PTX through influencing autophagy and apoptosis by modulating the PI3K-AKT-mTOR pathway and Bcl-2 family of proteins in A549 cells. Our findings demonstrated that the potential application of rhein as a candidate drug in combination with PTX is promising for treatment of the human lung cancer.
- Journal
- J Cell Physiol
- Publish Year
- 2020
- Experiment Subject
- rat; human; a549 cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Lung Cancer; Non-small-cell Lung Cancer
- Paper Title Cn
- Paper Title En
- Organic anion transporters and PI3K-AKT-mTOR pathway mediate the synergistic anticancer effect of pemetrexed and rhein
- Bilingual Status
- semi_complete