Downregulation of hepatic lipase is associated with decreased CD133 expression and clone formation in HepG2 cells

Abstract

The drug resistance of cancer remains a major obstacle to successful chemotherapy. New strategies for improving chemotherapeutic efficacy are urgently required. Recent studies have indicated that LIPC plays a role in promoting the liver metastasis of colorectal cancer. In the present study, we aimed to investigate the effects of LIPC on theproliferation and clone formation of colorectal cancer-derived cells, and chemoresistance in hepatoblastoma-derived HepG2 cells. The activity and expression of LIPC were determined in the cell lines by RT-qPCR and western blot analysis. HepG2 cells in which LIPC was knocked down by LIPC short hairpin RNA (shRNA) and control cells [shRNA control (shCON)] were established and analyzed for cell proliferation and colony formation rates. FACS analysis was used to explore the association between LIPC and the tumor-derived cell biomarker, CD133, and the percentages of CD133-positive cells were assessed by FACS. Additionally, shLIPC-and shCON-transfected cells were treated with various concentrations of doxorubicin and 5-floxuridine (5-FU), and cell viability was determined by MTT assay. mRNA levels in the shLIPC-and shCON-transfected cells were compared by cDNA microarray and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results revealed that the HepG2 cells exhibited a relatively higher LIPC activity and expression levels compared to the other colon cancer cell lines. The downregulation of LIPC in the HepG2 cells was associated with the decreased expression of CD133, decreased cell proliferation and colony formation, as well as increased resistance to chemotherapy. KEGG analysis of the cDNA microarray data revealed increased levels in the cell adhesion molecule (CAM) pathway, including CLDN10 and CLDN1, indicating that CAMs may play a role in LIPC-mediated tumor progression. The present findings indicate a potential role of LIPC as a promising therapeutic target in cancer.

Light controlled self‐escape capability of non‐cationic carbon nitride‐based nanosheets in lysosomes for hepatocellular carcinoma targeting stimulus‐responsive gene delivery

“…The liver, as a digestive organ, is rich in a large amount of lipase 48–51 . HepG2 cells also exhibit a relatively higher lipase activity and expression levels compared to the other colon cancer cell lines 52 . According to gel electrophoresis experiments, better DNA release ability of the Bio‐PEG‐CN/DNA complex was found under the coexistence of lipase and weak acidity.…”

“…[48][49][50][51] HepG2 cells also exhibit a relatively higher lipase activity and expression levels compared to the other colon cancer cell lines. 52 According to gel electrophoresis experiments, better DNA release ability of the Bio-PEG-CN/DNA complex was found under the coexistence of lipase and weak acidity. In the presence of acidic tumor microenvironment and abundant lipase in hepatoma cells (HepG2), the lipid bonds of Bio-PEG-CN material could be hydrolyzed more rapidly to realize the release of nucleic acid drugs at the lesion site.…”

LIPH promotes metastasis by enriching stem‐like cells in triple‐negative breast cancer

“…A recent study has shown that high expression of LIPG, another triglyceride lipase, is involved in TNBC metastasis through regulation of asymmetric cell division and maintenance of CSCs 16 . Moreover, down‐regulation of LIPC in HepG2 cells is associated with decreased expression of CD133, reduced cell proliferation and colony formation, as well as increased chemotherapy resistance 17 . CSCs are mainly responsible for the metastatic property of malignant cancers, 18 raising our interest in whether LIPH is involved in the behavioural regulation of CSCs.…”

“…16 Moreover, down-regulation of LIPC in HepG2 cells is associated with decreased expression of CD133, reduced cell proliferation and colony formation, as well as increased chemotherapy resistance. 17 CSCs are mainly responsible for the metastatic property of malignant cancers, 18 raising our interest in whether LIPH is involved in the behavioural regulation of CSCs. We investigated whether LIPH plays an important role in the maintenance of CSCs and promotes metastasis in breast cancer cells.…”