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. 2024 Jul 22;115(10):3333–3345. doi: 10.1111/cas.16292

FIGURE 4.

FIGURE 4

Co‐treatment with MCL‐1 inhibitor, AXL inhibitor, and lazertinib promoted apoptosis in EGFR‐mutant NSCLC cells. (A) PC‐9, HCC4011, and H1975 cells were treated with lazertinib (100 nmol/L), ONO7475 (100 nmol/L), MCL‐1 inhibitor S63845 (1 μmol/L), or combinations for 72 h. Cell growth was determined using MTT assays. *p < 0.05. (B) PC‐9, HCC4011, and H1975 cells were visualized using crystal violet staining following 9 days of treatment with lazertinib (100 nmol/L), ONO7475 (100 nmol/L), S63845 (1 μmol/L), or combinations where the drugs were replenished every 72 h. (C) PC‐9, HCC4011, and H1975 cells were treated with lazertinib (100 nmol/L) with or without ONO7475 (100 nmol/L), S63845 (1 μmol/L) for 48 h. The cells were lysed, and the indicated proteins were detected using western blotting. (D) Apoptotic cell percentages of PC‐9, HCC4011, and H1975 cells, which were double stained with annexin V and propidium iodide were detected using flow cytometry following treatment with lazertinib (100 nmol/L) with or without ONO7475 (100 nmol/L) and S63845 (1 μmol/L) for 48 h. *p < 0.05. (E) PC‐9 CDX tumors were treated with the vehicle control, 3 mg/kg lazertinib daily, 3 mg/kg lazertinib daily plus 10 mg/kg ONO‐7475 daily, and 3 mg/kg lazertinib daily plus 10 mg/kg ONO‐7475 daily plus 25 mg/kg S63845 twice a week (n = 6 per group). *Comparison of Lazertinib + ONO‐7475 with Lazertinib plus ONO‐7475 plus S63845 gave p < 0.05. (F) PC‐9 cells were treated with lazertinib (100 nmol/L) with or without ONO7475 (100 nmol/L) and S63845(1 μmol/L) for 48 h. Proteins were immunoprecipitated from the cell lysates and subjected to immunoblotting using anti‐MCL‐1, anti‐Bax, and anti‐Bak mAbs.