To evaluate the inhibitory effect of curcumin on sorafenib resistance in hepatocellular carcinoma (HCC) and unravel its regulatory mechanism.

Human sorafenib-resistant Hep3B-SR cell lines were successfully obtained by gradient concentration dosing method, and intervened by curcumin at a dose of 20 μg/ml. Long-chain non-coding RNA (LncRNA) expression microarray was used to screen the LncRNAs related to curcumin-intervened Hep3B-SR. qRT-PCR was employed to detect the changes of target LncRNA and the downstream related genes of CD44, MYC, JUN and FOS mRNA. The cell lines with knockdown and overexpression of target LncRNA were constructed. Cell colony and sphere formation assays were utilized to detect the stem-like changes of HCC. CCK-8 assay was adopted to detect the changes of IC₅₀ value of sorafenib. Western blot was performed to detect the changes of CD44, Wnt2, β-catenin, c-Myc proteins and the signaling pathway. The expression levels of mRNAs and proteins between two groups were compared by t test. The proliferation rate and IC₅₀ value of HCC cells among multiple groups were compared by one-way ANOVA and LSD-t test.

CCK8 assay showed that the average IC₅₀ value of sorafenib-resistant Hep3B-SR cell line was (8.4±1.1) μmol, significantly higher than (4.0±1.1) μmol of Hep3B cells (LSD-t=16.27, P<0.001) and (6.1±1.1) μmol of Hep3B-SR cells after curcumin (20 μg/ml) intervention (LSD-t=3.97, P<0.001). LncRNA expression microarray and qRT-PCR showed that curcumin could effectively up-regulate the expression of LncCCDC152 in drug-resistant HCC cells. Overexpression of LncCCDC152 could significantly down-regulate the sphere and colony formation ability of Hep3B HCC cells. LncCCDC152 could bind with transcriptional elongation regulator 1 (TCERG1), thus affecting the transcriptional activity and protein expression of the genes in the Wnt/β-catenin signaling pathway in cells.

Curcumin can suppress the sorafenib resistance of HCC, which targetedly inhibits the Wnt/β-catenin pathway probably by up-regulating the binding of LncCCDC152 with TCERG1 protein in HCC cells, thereby reducing stem-like activity of HCC and inhibiting sorafenib resistance.