Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma.
<p><b>(A and B)</b> Immunoblots of cleaved-PARP (c-PARP) and p-ERK detected in A375 (A) and A375R (B) cells after 48 h treatment of either DMSO, Vemurafenib, Volasertib, or a combination of Vemurafenib and Volasertib, respectively. <b>(C–E)</b> Percentages of apoptotic...
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2025
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| _version_ | 1849927642775552000 |
|---|---|
| author | Fengyi Mao (15073242) |
| author2 | Sai Wu (6096290) Derek B. Allison (15141675) Daheng He (9189701) Yifan Kong (4458616) Chaohao Li (15141681) Zhiguo Li (431917) Yanquan Zhang (14930570) Xinyi Wang (559030) Qiongsi Zhang (2818111) Chi Wang (131921) Xiaoqi Liu (45630) |
| author2_role | author author author author author author author author author author author |
| author_facet | Fengyi Mao (15073242) Sai Wu (6096290) Derek B. Allison (15141675) Daheng He (9189701) Yifan Kong (4458616) Chaohao Li (15141681) Zhiguo Li (431917) Yanquan Zhang (14930570) Xinyi Wang (559030) Qiongsi Zhang (2818111) Chi Wang (131921) Xiaoqi Liu (45630) |
| author_role | author |
| dc.creator.none.fl_str_mv | Fengyi Mao (15073242) Sai Wu (6096290) Derek B. Allison (15141675) Daheng He (9189701) Yifan Kong (4458616) Chaohao Li (15141681) Zhiguo Li (431917) Yanquan Zhang (14930570) Xinyi Wang (559030) Qiongsi Zhang (2818111) Chi Wang (131921) Xiaoqi Liu (45630) |
| dc.date.none.fl_str_mv | 2025-11-24T18:28:17Z |
| dc.identifier.none.fl_str_mv | 10.1371/journal.pbio.3003490.g006 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/figure/Inhibition_of_Polo-like_kinase_1_PLK1_synergizes_with_Vemurafenib_in_the_treatment_of_melanoma_/30697061 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Cell Biology Genetics Molecular Biology Developmental Biology Cancer Hematology Biological Sciences not elsewhere classified suppress tumor growth like kinase 1 crucial transcription factor cnc homolog 1 clinical database analysis shortened mice survival >< sup >< div >< p cutaneous melanoma based v600e </ sup patient survival pten </ ca </ ></ sup synergistic efficiency novel function negatively correlates genes involved cell cycle cancer progression cancer metabolism bach1 ), >- deficiency |
| dc.title.none.fl_str_mv | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma. |
| dc.type.none.fl_str_mv | Image Figure info:eu-repo/semantics/publishedVersion image |
| description | <p><b>(A and B)</b> Immunoblots of cleaved-PARP (c-PARP) and p-ERK detected in A375 (A) and A375R (B) cells after 48 h treatment of either DMSO, Vemurafenib, Volasertib, or a combination of Vemurafenib and Volasertib, respectively. <b>(C–E)</b> Percentages of apoptotic cells were measured by Annexin V staining after 48 h treatment of indicated drugs in human melanoma cells A375 (C), A375R (D), and SK-MEL-28 (E). Mean ± SD. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01 by unpaired Student <i>t</i> test. <i>n</i> = 3 biological replicates. <b>(F–H)</b> Metastatic ability was assessed by wound healing assay in A375 (F), A375R (G), and mMPI (H) cells, upon the 24 h treatment of indicated drugs. Mean ± SD. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01; *** <i>P</i> < 0.001 by unpaired Student <i>t</i> test. <i>n</i> = 3 biological replicates. <b>(I)</b> Transwell migration assay of A375 and A375R cells under drug treatmen<i>t</i>. <b>(J)</b> Growth curves of A375R-derived tumors. A375R cells (2 × 10<sup>6</sup>) were subcutaneously inoculated into the right flank region of female nude mice, followed by the administration with either vehicle, Vemurafenib (50 mg/kg body weight, oral gavage, once daily), Volasertib (10 mg/kg body weight, intraperitoneal injection, every 2 days), or a combination of both drugs. Mean ± SD. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01; *** <i>P</i> < 0.001 by unpaired Student <i>t</i> test. <i>n</i> = 4 mice from each experimental group. <b>(K and L)</b> Growth curves of mMC (K) and mMPI (L)-derived tumors. Female B6 mice were subcutaneously inoculated with mouse melanoma cells (1 × 10<sup>6</sup>) and administrated with the vehicle, Vemurafenib, Volasertib, or the combination of Vemurafenib and Volasertib after 1 week. Mean ± SD. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01; *** <i>P</i> < 0.001 by unpaired Student <i>t</i> test. <i>n</i> = 3 and 10, respectively, for each experimental group of mMC and mMPI. <b>(M)</b> Long-term survival analysis of <i>Braf</i><sup><i>CA/+</i></sup> <i>/ Pten</i><sup><i>loxp/loxp</i></sup> GEM mice upon the treatment of indicated drugs. <i>n</i> = 19, 11, 11, and 11, respectively, for the vehicle, Vemurafenib, Volasertib, or the dual treatment. The mice were euthanized when the tumor maximum diameter reached 14 mm. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01 by Log-rank (Mantel–Cox) test. <b>(N)</b> A proposed working model to reveal the mechanism of synergy between Vemurafenib and Volasertib. The figure was generated with BioRender.com. The data underlying the graphs shown in the figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003490#pbio.3003490.s014" target="_blank">S1 Data</a>.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_b98e355728757c6746bc0fd29c1d22f4 |
| identifier_str_mv | 10.1371/journal.pbio.3003490.g006 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/30697061 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma.Fengyi Mao (15073242)Sai Wu (6096290)Derek B. Allison (15141675)Daheng He (9189701)Yifan Kong (4458616)Chaohao Li (15141681)Zhiguo Li (431917)Yanquan Zhang (14930570)Xinyi Wang (559030)Qiongsi Zhang (2818111)Chi Wang (131921)Xiaoqi Liu (45630)Cell BiologyGeneticsMolecular BiologyDevelopmental BiologyCancerHematologyBiological Sciences not elsewhere classifiedsuppress tumor growthlike kinase 1crucial transcription factorcnc homolog 1clinical database analysisshortened mice survival>< sup ><div >< pcutaneous melanoma basedv600e </ suppatient survivalpten </ca </></ supsynergistic efficiencynovel functionnegatively correlatesgenes involvedcell cyclecancer progressioncancer metabolismbach1 ),>- deficiency<p><b>(A and B)</b> Immunoblots of cleaved-PARP (c-PARP) and p-ERK detected in A375 (A) and A375R (B) cells after 48 h treatment of either DMSO, Vemurafenib, Volasertib, or a combination of Vemurafenib and Volasertib, respectively. <b>(C–E)</b> Percentages of apoptotic cells were measured by Annexin V staining after 48 h treatment of indicated drugs in human melanoma cells A375 (C), A375R (D), and SK-MEL-28 (E). Mean ± SD. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01 by unpaired Student <i>t</i> test. <i>n</i> = 3 biological replicates. <b>(F–H)</b> Metastatic ability was assessed by wound healing assay in A375 (F), A375R (G), and mMPI (H) cells, upon the 24 h treatment of indicated drugs. Mean ± SD. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01; *** <i>P</i> < 0.001 by unpaired Student <i>t</i> test. <i>n</i> = 3 biological replicates. <b>(I)</b> Transwell migration assay of A375 and A375R cells under drug treatmen<i>t</i>. <b>(J)</b> Growth curves of A375R-derived tumors. A375R cells (2 × 10<sup>6</sup>) were subcutaneously inoculated into the right flank region of female nude mice, followed by the administration with either vehicle, Vemurafenib (50 mg/kg body weight, oral gavage, once daily), Volasertib (10 mg/kg body weight, intraperitoneal injection, every 2 days), or a combination of both drugs. Mean ± SD. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01; *** <i>P</i> < 0.001 by unpaired Student <i>t</i> test. <i>n</i> = 4 mice from each experimental group. <b>(K and L)</b> Growth curves of mMC (K) and mMPI (L)-derived tumors. Female B6 mice were subcutaneously inoculated with mouse melanoma cells (1 × 10<sup>6</sup>) and administrated with the vehicle, Vemurafenib, Volasertib, or the combination of Vemurafenib and Volasertib after 1 week. Mean ± SD. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01; *** <i>P</i> < 0.001 by unpaired Student <i>t</i> test. <i>n</i> = 3 and 10, respectively, for each experimental group of mMC and mMPI. <b>(M)</b> Long-term survival analysis of <i>Braf</i><sup><i>CA/+</i></sup> <i>/ Pten</i><sup><i>loxp/loxp</i></sup> GEM mice upon the treatment of indicated drugs. <i>n</i> = 19, 11, 11, and 11, respectively, for the vehicle, Vemurafenib, Volasertib, or the dual treatment. The mice were euthanized when the tumor maximum diameter reached 14 mm. n.s., <i>P</i> > 0.05; * <i>P</i> < 0.05; ** <i>P</i> < 0.01 by Log-rank (Mantel–Cox) test. <b>(N)</b> A proposed working model to reveal the mechanism of synergy between Vemurafenib and Volasertib. The figure was generated with BioRender.com. The data underlying the graphs shown in the figure can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.3003490#pbio.3003490.s014" target="_blank">S1 Data</a>.</p>2025-11-24T18:28:17ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.1371/journal.pbio.3003490.g006https://figshare.com/articles/figure/Inhibition_of_Polo-like_kinase_1_PLK1_synergizes_with_Vemurafenib_in_the_treatment_of_melanoma_/30697061CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/306970612025-11-24T18:28:17Z |
| spellingShingle | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma. Fengyi Mao (15073242) Cell Biology Genetics Molecular Biology Developmental Biology Cancer Hematology Biological Sciences not elsewhere classified suppress tumor growth like kinase 1 crucial transcription factor cnc homolog 1 clinical database analysis shortened mice survival >< sup >< div >< p cutaneous melanoma based v600e </ sup patient survival pten </ ca </ ></ sup synergistic efficiency novel function negatively correlates genes involved cell cycle cancer progression cancer metabolism bach1 ), >- deficiency |
| status_str | publishedVersion |
| title | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma. |
| title_full | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma. |
| title_fullStr | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma. |
| title_full_unstemmed | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma. |
| title_short | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma. |
| title_sort | Inhibition of Polo-like kinase 1 (PLK1) synergizes with Vemurafenib in the treatment of melanoma. |
| topic | Cell Biology Genetics Molecular Biology Developmental Biology Cancer Hematology Biological Sciences not elsewhere classified suppress tumor growth like kinase 1 crucial transcription factor cnc homolog 1 clinical database analysis shortened mice survival >< sup >< div >< p cutaneous melanoma based v600e </ sup patient survival pten </ ca </ ></ sup synergistic efficiency novel function negatively correlates genes involved cell cycle cancer progression cancer metabolism bach1 ), >- deficiency |