Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway.

Background: Elevated level of interleukin-8 (IL-8) promotes hepatocellular carcinoma (HCC) development and contributes to poor prognosis. Previously, we have proved that Dicer inhibits HCC progression. In this study, we evaluated the potential interaction between IL-8 and Dicer as well as their influence on HCC. Methods: Hepatocellular carcinoma cells of SMMC-7721 were divided into 2 groups for subsequent analysis: pCMV-Dicer group for Dicer-overexpressing lentivirus transfected cells (pCMV-Dicer cells) and pCMV-NC group for empty lentivirus transfected cells (pCMV-NC cells). Cell Counting kit-8 (CCK8), wound healing, and transwell were used to evaluate the inhibitory effect of Dicer overexpression on proliferation, migration, and invasion of HCC cells. The level of IL-8 was measured by flow cytometry bead-based immunoassays. Male nude BALB/c mice injected with pCMV-Dicer or pCMV-NC cell suspensions was used for transplant of HCC tumor. Results: We found that the secretion of IL-8 was reduced in the medium of pCMV-Dicer cells (P =.027). Recombinant human IL-8 (rhIL-8) reversed the inhibitory effect of Dicer on proliferation (P <.01), migration (P =.003), and invasion (P =.001), whereas IL-8 inhibitor of reparixin enhanced inhibitory effect of Dicer on proliferation (P <.05), migration (P =.008), and invasion (P =.000). Lenvatinib downregulated the IL-8 level of HCC cells (P =.000) as well as promote Dicer-induced inhibition for HCC cells referring to proliferation (P <.05), migration (P =.000), and invasion (P =.000). Animal experiments also demonstrated that Dicer cooperated with lenvatinib to inhibit the growth of HCC tumors (P <.05). Conclusions: Dicer cooperated with lenvatinib to inhibit HCC growth via downregulating IL-8, and Dicer displayed its potential capability to enhance the anti-tumor effect of lenvatinib. [ABSTRACT FROM AUTHOR]