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. 2023 Feb 8;15(4):1092. doi: 10.3390/cancers15041092

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© 2023 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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PAI-1 inhibition limited tolerance to osimertinib and regrowth in the subcutaneous tumor model. (A) H1975 cell tumor bearing mice were treated with vehicle (vehicle group) or osimertinib (osimertinib group), as described in the Methods Section (n = 6 each). Tumor volumes were measured over time from the start of treatment. Mean tumor volumes are shown with standard error bars; * p < 0.05 compared to the vehicle group (Student’s t-test). Representative images of tumor specimens stained with antibodies against human PAI-1 via immunohistochemistry. (B) The upper row is arranged with hematoxylin and eosin (HE) staining, and the lower row is arranged with PAI-1 immunostaining images. Tumors of the vehicle group and osimertinib group are shown; bar: 50 µm. (C) The proportion of PAI-1-positive areas between tumors of the vehicle group and osimertinib group. Data represent the mean values of six samples with standard error bars; * p < 0.05 compared to vehicle group (Student’s t-test). (D) H1975 cell tumor bearing mice were treated with vehicle (vehicle group), SK-216 (SK-216 group), osimertinib (osimertinib group), and osimertinib with SK-216 (osimertinib + SK-216 group), as described in the Methods Section (n = 8 each). A graph of the osimertinib group and osimertinib + SK-216 group is also shown in the upper right corner. Tumor volumes were measured over time from the start of treatment. Mean tumor volumes are shown with standard error bars; * p < 0.05 compared to the osimertinib group (one-way ANOVA with Tukey’s test). (E) The upper row is arranged with hematoxylin and eosin (HE) staining, and the lower row is arranged with PAI-1 immunostaining images. Tumors in the vehicle group, osimertinib group, and osimertinib + SK-216 group are shown; bar: 100 µm. (F) The proportion of PAI-1-positive area between tumors in the vehicle group and osimertinib group. Data represent the mean values of eight samples with standard error bars; * p < 0.05 compared with the vehicle group (Student’s t-test).

PAI-1 inhibition limited tolerance to osimertinib and regrowth in the subcutaneous tumor model. (A) H1975 cell tumor bearing mice were treated with vehicle (vehicle group) or osimertinib (osimertinib group), as described in the Methods Section (n = 6 each). Tumor volumes were measured over time from the start of treatment. Mean tumor volumes are shown with standard error bars; * p < 0.05 compared to the vehicle group (Student’s t-test). Representative images of tumor specimens stained with antibodies against human PAI-1 via immunohistochemistry. (B) The upper row is arranged with hematoxylin and eosin (HE) staining, and the lower row is arranged with PAI-1 immunostaining images. Tumors of the vehicle group and osimertinib group are shown; bar: 50 µm. (C) The proportion of PAI-1-positive areas between tumors of the vehicle group and osimertinib group. Data represent the mean values of six samples with standard error bars; * p < 0.05 compared to vehicle group (Student’s t-test). (D) H1975 cell tumor bearing mice were treated with vehicle (vehicle group), SK-216 (SK-216 group), osimertinib (osimertinib group), and osimertinib with SK-216 (osimertinib + SK-216 group), as described in the Methods Section (n = 8 each). A graph of the osimertinib group and osimertinib + SK-216 group is also shown in the upper right corner. Tumor volumes were measured over time from the start of treatment. Mean tumor volumes are shown with standard error bars; * p < 0.05 compared to the osimertinib group (one-way ANOVA with Tukey’s test). (E) The upper row is arranged with hematoxylin and eosin (HE) staining, and the lower row is arranged with PAI-1 immunostaining images. Tumors in the vehicle group, osimertinib group, and osimertinib + SK-216 group are shown; bar: 100 µm. (F) The proportion of PAI-1-positive area between tumors in the vehicle group and osimertinib group. Data represent the mean values of eight samples with standard error bars; * p < 0.05 compared with the vehicle group (Student’s t-test).