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. 2021 Oct;10(10):3995–4011. doi: 10.21037/tlcr-21-767

Figure 4.

Figure 4

Inhibition of USP5 activity suppresses non-small cell lung cancer (NSCLC) cell proliferation and xenograft tumor growth. (A) The chemical structure of the USP5 inhibitors, WP1130 and EOAI3402143 (G9). (B) Both WP1130 and G9 inhibited the cell viability of A549 and H1299 cells in a concentration-dependent manner in vitro. Representative data under 48 hours of treatment are shown. (C) The effects of WP1130 and G9 on the expression levels of CCND1 and USP5 in NSCLC cells. A549 and H1299 cells were subjected to WP1130 or G9 treatment for 24 hours, followed by immunoblotting assay as indicated above. (D-G) G9 suppresses NSCLC tumor growth in nude mice. Tumor volume (D), images of tumor-bearing mice (E) and A549 xenograft tumors (F), and tumor weight (G) are shown. (H-L) G9 (15 mg/kg) exerted no significant toxicity in nude mice. The body weight of the mice (H) and biological analyses of the levels of alanine aminotransferase (I), aspartate aminotransferase (J), creatinine (K), and urea (L) in the blood of the mice are shown. (M,N) Immunohistochemical (IHC) analysis of the protein levels of CCND1 and USP5 in tumor tissues. Representative IHC images (upper: ×40; lower: ×200) (M) and scores (N) are shown. *, P<0.05; **, P<0.01; ***, P<0.001, Student’s t-test.