Figure 4 from Bcl-xL Is a Key Mediator of Apoptosis Following KRAS<sup>G12C</sup> Inhibition in <i>KRAS<sup>G12C</sup></i>-mutant Colorectal Cancer

Figure 4 from Bcl-xL Is a Key Mediator of Apoptosis Following KRAS<sup>G12C</sup> Inhibition in <i>KRAS<sup>G12C</sup></i>-mutant Colorectal Cancer

<p>High-throughput drug screen reveals that pharmacologic inhibition of Bcl-xL synergizes with KRAS<sup>G12C</sup> inhibition in <i>KRAS</i><sup>G12C</sup> MT colorectal cancer. <b>A,</b> SW837 and SNU1411 cells were cotreated with 1 μmol/L AZ’15...

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Бібліографічні деталі
Автор:	Hajrah Khawaja (15090810) (author)
Інші автори:	Rebecca Briggs (15090813) (author), Cheryl H. Latimer (15090816) (author), Mustasin Rassel (15090819) (author), Daryl Griffin (15090822) (author), Lyndsey Hanson (15090825) (author), Alberto Bardelli (15046646) (author), Frederica Di Nicolantonio (15090828) (author), Simon S. McDade (14939679) (author), Christopher J. Scott (15090831) (author), Shauna Lambe (15090834) (author), Manisha Maurya (15090837) (author), Andreas U. Lindner (15033719) (author), Jochen H.M. Prehn (15033731) (author), Jose Sousa (15090840) (author), Chris Winnington (15090843) (author), Melissa J. LaBonte (15090846) (author), Sarah Ross (15090849) (author), Sandra Van Schaeybroeck (15090852) (author)
Опубліковано:	2025
Предмети:	Cancer Cancer Biology Therapeutic Research and Development Drug Resistance Novel mechanisms Gastrointestinal Cancers Colorectal cancer Oncogenes & Tumor Suppressors Kras
Теги:	Додати тег Немає тегів, Будьте першим, хто поставить тег для цього запису!

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Резюме:	<p>High-throughput drug screen reveals that pharmacologic inhibition of Bcl-xL synergizes with KRAS<sup>G12C</sup> inhibition in <i>KRAS</i><sup>G12C</sup> MT colorectal cancer. <b>A,</b> SW837 and SNU1411 cells were cotreated with 1 μmol/L AZ’1569 alone or combined with a panel of 45 small-molecule inhibitors for 72 hours and cell viability assessed using the CTG assay. Three concentrations per drug were tested (Supplementary Table S2). Cell viability was analyzed using a CTG assay. Scatter plot showing rZ for each compound concentration used in the drug screen. Negative rZ-scores indicate agents that sensitize to AZ’1569, and <i>vice versa</i>. Dashed lines on graphs indicate values of 1.5 and −1.5. Venn diagram indicates number of compounds (past a threshold of rZ = −1.5) that resulted in sensitization to AZ’1569 in both cell lines. <b>B,</b> CTG cell viability assays in <i>KRAS</i><sup>G12C</sup> MT colorectal cancer cells cotreated with AZ’1569 and ABT-737 for 72 hours. CI values were calculated to evaluate the nature of interaction. Absolute cell viability for AZ’1569/ABT-737 combinations in SW847 and SNU1411 cell lines are also shown. Dashed lines on graphs represent 50% cell viability. <b>C,</b> PARP, cleaved C9, cleaved C8, cleaved C3, and KRAS expression levels in <i>KRAS</i><sup>G12C</sup> MT colorectal cancer cells cotreated with AZ’1569 and ABT-737 for 48 hours (24 hours for RW7213, SW1463, and V481 cells). CM = combination. <b>D,</b><i>KRAS</i><sup>G12C</sup> MT colorectal cancer cells were treated with AZ’1569 alone or combined with cetuximab or ABT-737 (0.25 μmol/L for C106, LIM2099, SNU1411; 0.5 μmol/L for SW837, V481, RW7213 and 2.5 μmol/L for SW1463) for 48 hours (24 hours for C106 cells) and PARP, cleaved C9, cleaved C8, and cleaved C3 determined by WB.</p>