Farnesyl-diphosphate farnesyltransferase 1 promotes growth of colorectal cancer cells with dependence on tumor immune microenvironment

Abstract

Objective To investigate the effects of farnesyl-diphosphate farnesyltransferase 1 (FDFT1) on the growth of colorectal cancer (CRC) cell line MC-38 in vitro and in mouse models of colorectal peritoneal metastasis and xenograft tumor. Methods The expression of FDFT1 in 275 CRC samples and 349 normal tissue samples, as well as the immunohistochemical expression level of FDFT1 in human CRC tissues were analyzed using online databases Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas, respectively. FDFT1-silenced CRC cell line MC-38 was constructed by lentivirus-mediated short hairpin RNA (shRNA) to obtain stable cells with low expression of FDFT1 (sh-FDFT1), and blank control cells (sh-NC) was also constructed. The knockdown effect was subsequently verified by Western blotting and RT-qPCR. Cell counting kit-8 (CCK-8) assay, flow cytometry and transwell assay were performed to observe the effects of FDFT1 knockdown on the proliferation, apoptosis and migration of MC-38 cells, respectively. In addition, intraperitoneal implantation models of colorectal cancer were established using C57BL/6 mice and severe immunodeficient NCG mice, and subcutaneous transplantation tumor model was also constructed using C57BL/6 mice. The effects of FDFT1 silencing on tumor growth in vivo were observed in 14 d after transplantation. Results Database analysis showed that FDFT1 expression was higher in CRC tissues than normal tissues (P 0.05). Conclusion FDFT1 depends on the tumor immune microenvironment in the promotion of the growth of CRC cells in vivo.

Keywords

• farnesyl-diphosphate farnesyltransferase 1
• colorectal cancer
• immune microenvironment
• mc-38 cells