@article{Chi2021a,
abstract = {Background: Inhibition of nuclear import via Karyopherin beta 1 (Kpn$\beta$1) shows potential as an anti-cancer approach. This study investigated the use of nuclear import inhibitor, INI-43, in combination with cisplatin. Methods: Cervical cancer cells were pre-treated with INI-43 before treatment with cisplatin, and MTT cell viability and apoptosis assays performed. Activity and localisation of p53 and NF$\kappa$B was determined after co-treatment of cells. Results: Pre-treatment of cervical cancer cells with INI-43 at sublethal concentrations enhanced cisplatin sensitivity, evident through decreased cell viability and enhanced apoptosis. Kpn$\beta$1 knock-down cells similarly displayed increased sensitivity to cisplatin. Combination index determination using the Chou-Talalay method revealed that INI-43 and cisplatin engaged in synergistic interactions. p53 was found to be involved in the cell death response to combination treatment as its inhibition abolished the enhanced cell death observed. INI-43 pre-treatment resulted in moderately stabilized p53 and induced p53 reporter activity, which translated to increased p21 and decreased Mcl-1 upon cisplatin combination treatment. Furthermore, cisplatin treatment led to nuclear import of NF$\kappa$B, which was diminished upon pre-treatment with INI-43. NF$\kappa$B reporter activity and expression of NF$\kappa$B transcriptional targets, cyclin D1, c-Myc and XIAP, showed decreased levels after combination treatment compared to single cisplatin treatment and this associated with enhanced DNA damage. Conclusions: Taken together, this study shows that INI-43 pre-treatment significantly enhances cisplatin sensitivity in cervical cancer cells, mediated through stabilization of p53 and decreased nuclear import of NF$\kappa$B. Hence this study suggests the possible synergistic use of nuclear import inhibition and cisplatin to treat cervical cancer.},
author = {Chi, R.-P.A. and van der Watt, P. and Wei, W. and Birrer, M.J. and Leaner, V.D.},
doi = {10.1186/s12885-021-07819-3},
journal = {BMC Cancer},
number = {1},
title = {{Inhibition of Kpn$\beta$1 mediated nuclear import enhances cisplatin chemosensitivity in cervical cancer}},
volume = {21},
year = {2021}
}

{"_id":"wayAwQjL5n2PogGF2","bibbaseid":"chi-vanderwatt-wei-birrer-leaner-inhibitionofkpn1mediatednuclearimportenhancescisplatinchemosensitivityincervicalcancer-2021","author_short":["Chi, R.","van der Watt, P.","Wei, W.","Birrer, M.","Leaner, V."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background: Inhibition of nuclear import via Karyopherin beta 1 (Kpn$β$1) shows potential as an anti-cancer approach. This study investigated the use of nuclear import inhibitor, INI-43, in combination with cisplatin. Methods: Cervical cancer cells were pre-treated with INI-43 before treatment with cisplatin, and MTT cell viability and apoptosis assays performed. Activity and localisation of p53 and NF$κ$B was determined after co-treatment of cells. Results: Pre-treatment of cervical cancer cells with INI-43 at sublethal concentrations enhanced cisplatin sensitivity, evident through decreased cell viability and enhanced apoptosis. Kpn$β$1 knock-down cells similarly displayed increased sensitivity to cisplatin. Combination index determination using the Chou-Talalay method revealed that INI-43 and cisplatin engaged in synergistic interactions. p53 was found to be involved in the cell death response to combination treatment as its inhibition abolished the enhanced cell death observed. INI-43 pre-treatment resulted in moderately stabilized p53 and induced p53 reporter activity, which translated to increased p21 and decreased Mcl-1 upon cisplatin combination treatment. Furthermore, cisplatin treatment led to nuclear import of NF$κ$B, which was diminished upon pre-treatment with INI-43. NF$κ$B reporter activity and expression of NF$κ$B transcriptional targets, cyclin D1, c-Myc and XIAP, showed decreased levels after combination treatment compared to single cisplatin treatment and this associated with enhanced DNA damage. Conclusions: Taken together, this study shows that INI-43 pre-treatment significantly enhances cisplatin sensitivity in cervical cancer cells, mediated through stabilization of p53 and decreased nuclear import of NF$κ$B. Hence this study suggests the possible synergistic use of nuclear import inhibition and cisplatin to treat cervical cancer.","author":[{"propositions":[],"lastnames":["Chi"],"firstnames":["R.-P.A."],"suffixes":[]},{"propositions":["van","der"],"lastnames":["Watt"],"firstnames":["P."],"suffixes":[]},{"propositions":[],"lastnames":["Wei"],"firstnames":["W."],"suffixes":[]},{"propositions":[],"lastnames":["Birrer"],"firstnames":["M.J."],"suffixes":[]},{"propositions":[],"lastnames":["Leaner"],"firstnames":["V.D."],"suffixes":[]}],"doi":"10.1186/s12885-021-07819-3","journal":"BMC Cancer","number":"1","title":"Inhibition of Kpn$β$1 mediated nuclear import enhances cisplatin chemosensitivity in cervical cancer","volume":"21","year":"2021","bibtex":"@article{Chi2021a,\nabstract = {Background: Inhibition of nuclear import via Karyopherin beta 1 (Kpn$\\beta$1) shows potential as an anti-cancer approach. This study investigated the use of nuclear import inhibitor, INI-43, in combination with cisplatin. Methods: Cervical cancer cells were pre-treated with INI-43 before treatment with cisplatin, and MTT cell viability and apoptosis assays performed. Activity and localisation of p53 and NF$\\kappa$B was determined after co-treatment of cells. Results: Pre-treatment of cervical cancer cells with INI-43 at sublethal concentrations enhanced cisplatin sensitivity, evident through decreased cell viability and enhanced apoptosis. Kpn$\\beta$1 knock-down cells similarly displayed increased sensitivity to cisplatin. Combination index determination using the Chou-Talalay method revealed that INI-43 and cisplatin engaged in synergistic interactions. p53 was found to be involved in the cell death response to combination treatment as its inhibition abolished the enhanced cell death observed. INI-43 pre-treatment resulted in moderately stabilized p53 and induced p53 reporter activity, which translated to increased p21 and decreased Mcl-1 upon cisplatin combination treatment. Furthermore, cisplatin treatment led to nuclear import of NF$\\kappa$B, which was diminished upon pre-treatment with INI-43. NF$\\kappa$B reporter activity and expression of NF$\\kappa$B transcriptional targets, cyclin D1, c-Myc and XIAP, showed decreased levels after combination treatment compared to single cisplatin treatment and this associated with enhanced DNA damage. Conclusions: Taken together, this study shows that INI-43 pre-treatment significantly enhances cisplatin sensitivity in cervical cancer cells, mediated through stabilization of p53 and decreased nuclear import of NF$\\kappa$B. Hence this study suggests the possible synergistic use of nuclear import inhibition and cisplatin to treat cervical cancer.},\nauthor = {Chi, R.-P.A. and van der Watt, P. and Wei, W. and Birrer, M.J. and Leaner, V.D.},\ndoi = {10.1186/s12885-021-07819-3},\njournal = {BMC Cancer},\nnumber = {1},\ntitle = {{Inhibition of Kpn$\\beta$1 mediated nuclear import enhances cisplatin chemosensitivity in cervical cancer}},\nvolume = {21},\nyear = {2021}\n}\n","author_short":["Chi, R.","van der Watt, P.","Wei, W.","Birrer, M.","Leaner, V."],"key":"Chi2021a","id":"Chi2021a","bibbaseid":"chi-vanderwatt-wei-birrer-leaner-inhibitionofkpn1mediatednuclearimportenhancescisplatinchemosensitivityincervicalcancer-2021","role":"author","urls":{},"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-9gwO2GBrWfUK-fFo05cgfzXdRK_w9xL","dataSources":["9bX4N36CTXtCXNFMd","6GMFi5DCojy3jHY44"],"keywords":[],"search_terms":["inhibition","kpn","mediated","nuclear","import","enhances","cisplatin","chemosensitivity","cervical","cancer","chi","van der watt","wei","birrer","leaner"],"title":"Inhibition of Kpn$β$1 mediated nuclear import enhances cisplatin chemosensitivity in cervical cancer","year":2021}