Objective To investigate the inhibitory effect and molecular mechanism of Huaier granule on the growth of sorafenib resistant hepatocellular carcinoma (HCC) cells.

Methods The gradient concentration of Huaier granule was used to treat HCC cells, and the effect of Huaier granule on the proliferation, migration and invasion of sorafenib resistant HCC cells was analyzed. Bioinformatics methods were used to analyze the possible interaction between microRNA-31-5p (miR-31-5p) and sprouty-related proteins with an EVH1 domain 1 (SPRED1). The expression levels of miR-31-5p and SPRED1 in HCC cells were detected by real time fluorescence quantitative polymerase chain reaction (qRT-PCR); cell viability, proliferation, migration, invasion and apoptosis were detected by CCK-8, colony formation, scratch healing, Transwell and flow cytometry; RNA immunoprecipitation (RIP) assay and dual luciferase assay were used to verify the binding relationship between miR-31-5p and SPRED1.

Results Huaier granule could significantly inhibit the proliferation, migration and invasion of sorafenib resistant HCC cells, and induce apoptosis. Bioinformatics analysis showed that miR-31-5p was highly expressed in HCC, and Huaier granule was able to down-regulate the expression of miR-31-5p, inhibit the proliferation and metastasis of sorafenib resistant HCC cells, and induce apoptosis; miR-31-5p showed a targeted inhibition effect on the expression of SPRED1. SPRED1 was down-regulated in HCC, and overexpression of SPRED1 was able to reverse the promoting effect of overexpression of miR-31-5p on proliferation and metastasis of sorafenib resistant HCC.

Conclusion Huaier granule can inhibit sorafenib resistant HCC metastasis through the miR-31-5p/SPRED1 axis, indicating that Huaier granule has the potential to be used as a novel drug for HCC treatment.