Sinomenine hydrochloride enhancement of the inhibitory effects of anti-transferrin receptor antibody-dependent on the COX-2 pathway in human hepatoma cells

Abstract

Transferrin receptor (TfR) has been used as a target for the antibody-based therapy of cancer due to its higher expression in tumors relative to normal tissues. Great potential has been shown by anti-TfR antibodies combined with chemotherapeutic drugs as a possible cancer therapeutic strategy. In our study, we investigated the anti-tumor effects of anti-TfR monoclonal antibody (mAb) alone or in combination with sinomenine hydrochloride in vitro. Results suggested that anti-TfR mAb or sinomenine hydrochloride could induce apoptosis, inhibit proliferation, and affect the cell cycle. A synergistic effect was found in relation to tumor growth inhibition and the induction of apoptosis when anti-TfR mAb and sinomenine hydrochloride were used simultaneously. The expression of COX-2 and VEGF protein in HepG2 cells treated with anti-TfR mAb alone was increased in line with increasing dosage of the agent. In contrast, COX-2 expression was dramatically decreased in HepG2 cells treated with sinomenine hydrochloride alone. Furthermore, we demonstrated that the inhibitory effects of sinomenine hydrochloride and anti-TfR mAb administered in combination were more prominent than when the agents were administered singly. To sum up, these results showed that the combined use of sinomenine hydrochloride and anti-TfR mAb may exert synergistic inhibitory effects on human hepatoma HepG2 cells in a COX-2-dependent manner. This finding provides new insight into how tumor cells overcome the interference of iron intake to survive and forms the basis of a new therapeutic strategy involving the development of anti-TfR mAb combined with sinomenine hydrochloride for liver cancer.

Sinomenine Sensitizes Multidrug-Resistant Colon Cancer Cells (Caco-2) to Doxorubicin by Downregulation of MDR-1 Expression

“…2). Some studies have indicated that sinomenine inhibited the expression of COX-2 [30], [31]. Consistent with these results, our findings manifested that sinomenine downregulated COX-2 expression in MDR-caco-2 cells (Fig.…”

Endocytosis of a Functionally Enhanced GFP-Tagged Transferrin Receptor in CHO Cells

“…Cell lysates were centrifuged at 12000 rpm for 5 min and the supernatants were divided on 12% polyacrylamide gel. The transferred membrane was immunoblotted with mouse anti-hTfR monoclonal antibody (anti-hTfR mAb, produced by our laboratory [ 6 – 8 ]) overnight at 4°C followed by HRP-labeled goat anti mouse Ab (Southern Biotech, Birmingham, USA) for 1h at 37°C. Proteins were detected using ECL kit (Pierce, Rockford, USA).…”

Transferrin-targeted magnetic/fluorescence micelles as a specific bi-functional nanoprobe for imaging liver tumor

“…Iron overload conditions contribute to several pathological conditions including iron overload-related hepatic cancer [24]. The TfR expression level is often higher in the tumor tissue than the normal tissue [20]. Therefore, Tf can be used as the ligand for targeting liver tumor.…”

“…Transferrin (Tf) is one of the most widely used tumor-targeted ligands because Tf receptors (TfRs) are over-expressed on malignant cells and play a key role in cellular iron uptake through the interaction with Tf [17]. Moreover, the expression level of TfRs has been suggested to correlate with tumor stage or cancer progression [18-20]. …”