Drug Combination Details
| General Information of the Combination (ID: C07139) | |||||
|---|---|---|---|---|---|
| Name | Fisetin NP Info | + | Sorafenib Drug Info | ||
| Structure |
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| Disease |
Melanoma
[ICD-11: 2C30]
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Investigative | [1] | ||
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Cervical cancer
[ICD-11: 2C77]
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Investigative | [2] | |||
| Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally | ||||||
|---|---|---|---|---|---|---|
| α. Enhancing Drug Efficacy by This Combination | ||||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Experiment 1 Reporting the Effect of This Combination | [3] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | AKT1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BAK | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | ERK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | ERK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MCL1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | MEK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | MEK2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | mTOR | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | PARP1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | PIK3CB | Molecule Info |
Pathway MAP
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| In-vitro Model | A-375 | CVCL_0132 | Amelanotic melanoma | Homo sapiens | ||
| RPMI-7951 | CVCL_1666 | Melanoma | Homo sapiens | |||
| In-vivo Model | Mice were subcutaneously inoculated with 0.1ml of 2.5*106 A375 cells or 5*106 SK-MEL-28 cells (prepared in a 50ul media + 50ul matrigel) in each flank to initiate tumor growth. | |||||
| Experimental
Result(s) |
Fisetin potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. | |||||
| Experiment 2 Reporting the Effect of This Combination | [2] | |||||
| Molecule(s)
Regulation |
Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP8 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | PARP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TRAIL-R2 | Molecule Info |
Pathway MAP
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| In-vitro Model | HeLa | CVCL_0030 | Endocervical adenocarcinoma | Homo sapiens | ||
| In-vivo Model | For the in vivo experiments, 1*106 HeLa cells (diluted in Matrigel) were established by subcutaneous injec tion into the animal's right flank. | |||||
| Experimental
Result(s) |
The combination of fisetin and sorafenib exerted better synergistic effects in vitro and in vivo than either agent used alone against human cervical cancer, and this synergism was based on apoptotic potential through a mitochondrial- and DR5-dependent caspase-8/caspase-3 signaling pathway. | |||||
| Experiment 3 Reporting the Effect of This Combination | [1] | |||||
| Molecule(s)
Regulation |
Up-regulation | Expression | CDH1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CDH2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | FN1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MMP-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MMP-9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | SNAI1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | SNAI2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | TWIST1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | VIM | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | ZEB1 | Molecule Info |
Pathway MAP
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| In-vitro Model | A-375 | CVCL_0132 | Amelanotic melanoma | Homo sapiens | ||
| SK-MEL-28 | CVCL_0526 | Cutaneous melanoma | Homo sapiens | |||
| In-vivo Model | Female athymic nude mice of five weeks age were subcutaneously transplanted with A375 or SK-MEL-28 cells (2.5 * 106 A375 cells in 50 ul DMEM + 50 ul matrigel or 5 * 106 SK-MEL-28 cells in 50 ul RPMI + 50 ul matrigel) in each flank. | |||||
| Experimental
Result(s) |
Fisetin potentiates the anti-invasive and anti-metastatic effects of sorafenib. | |||||
