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. 2022 Jul 5;12:936145. doi: 10.3389/fonc.2022.936145

Figure 5.

Figure 5

Effect of GHRA on response of syngeneic mouse hepatocellular carcinoma tumors to sorafenib treatment in vivo. (A) Mouse Hepa1-6 hepatocellular carcinoma (HCC) cells respond to bovine GH stimulation in culture showing increased cell viability and STAT5 activation after 72 hours (A) as well as increase in the EC50 dose of sorafenib (B). Additionally, GH treatment increased ABC transporter levels in the cultured Hepa1-6 cells (C). Mouse Hepa1-6 cells grafted subcutaneously on the right flank of syngeneic C57BL6/J wild-type (WT) and GHA mice (transgenic for bGH G119K GHR antagonist) (n=6). The changes in tumor volume (Hepa1-6 in WT and GHA mice) from digital caliper measurement (D) and post-dissection tumor mass (E) show suppressed tumor growth and improved tumoral response to sorafenib in the GHA mice. (F) Spearman correlation analysis for transcript levels of GHR and ABC transporter and IGF1R and ABC transporters in the tumor of 371 HCC patients in the TCGA cohort. (G) Serum IGF1 levels of Hepa1-6 tumor-bearing GHA mice are significantly lower than that of tumor-bearing WT mice. (H–J) Correlation of overall survival probability of 371 HCC patients in the TCGA cohort with RNA expression of IGF1R (H), or ABCB1 (I), or ABCC1 (J). (*p < 0.05, ***p < 0.001, mouse studies – repeated measure using SPSS; other assays - Students t test, n = 3).