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Figure 4 | Molecular Cancer

Figure 4

From: Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1

Figure 4

LRRK2-IN-1 downregulates DCLK1 expression and downstream target c-Myc. LRRK2-in-1 downregulates DCLK1 mRNA expression in a dose and time-dependent manner in AsPC-1 cells (A). LRRK2-IN-1 significantly downregulates DCLK1 protein expression at 24 and 48 h and downregulates protein expression of DCLK1 downstream target c-MYC (B-C). NCBI GEO data demonstrating inhibition of MAPK7/ERK5 with 10 μM U0126 resulting in downregulation of DCLK1 gene expression in SW480 cells (D). Treatment of AsPC-1 cells with 10 μM U0126 downregulates DCLK1 as well as shared downstream target c-MYC’s mRNA and protein levels. However, whereas combined treatment with this dose of U0126 (10 min pretreatment) and 5 μM LRRK2-IN-1 results in synergistic downregulation of c-MYC, DCLK1 is unaffected or slightly upregulated suggesting that U0126 and LRRK2-IN-1 may regulate DCLK1 mRNA and protein expression by the same mechanism of action (E-G).

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Molecular Cancer

ISSN: 1476-4598