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PMX 500 – CCRF-CEM Vincristine resistance – X-gal senescence staining

PMX 500 – CCRF-CEM Vincristine resistance – X-gal senescence staining. PMX 700 – U373V/M/VR cells. Is resistance to TMZ sustained following withdrawal of selection media?

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PMX 500 – CCRF-CEM Vincristine resistance – X-gal senescence staining

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  1. PMX 500 – CCRF-CEM Vincristine resistance – X-gal senescence staining

  2. PMX 700 – U373V/M/VR cells Is resistance to TMZ sustained following withdrawal of selection media? Grown with/without selection media (i.e. G418 for U373V and U373M or TMZ for U373VR) for 7d prior to setting up MTT assay. U373M cells maintain resistance despite 42 days w/o selection media.

  3. PMX 700 – PARP Potentiation HCT116 cells Treated with PARP inhibitor (ABT888, AG014699 or AZD2281) for 1 h followed by addition of Temozolomide (2, 5,10, 20 or 100 mM , PMX-000268, PMX-000495, PMX-000559, PMX-000561 or PMX-000568 (2, 5 or 10 mM) for a further 16 h. Media aspirated and replaced with drug free media. Cells allowed to grow for a further 72h prior to MTT assay. Growth curves generated and IC50’s calculated. PF50s calculated: PARP inhibitor IC50 PARP inhibitor + alkylating agent IC50 Toxicity of alkylating agents assessed. ** ** ** * ** * p<0.01 ** p<0.05 ANOVA vs control (Con) Con 2 5 10 20 100 1 2 5 10 1 2 5 10 1 2 5 10 1 2 5 10 1 2 5 10 (mM) Temozolomide PMX-000268 PMX-000495 PMX-000559 PMX-000561 PMX-000568

  4. PMX 700 – PARP Potentiation • 2 5 10 20 2 5 10 2 5 10 2 5 10 2 5 10 2 5 10 (mM) • Temozolomide PMX-000268 PMX-000495 PMX-000559 PMX-000561 PMX-000568 • 1 2 3 0 1 3 1 1 3 1 1 3 1 1 3 1 1 3 (n) ABT888 • 1 2 3 3 0 1 2 1 1 2 1 1 2 1 1 2 1 1 2 (n) AG014699/AZD2281

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