Rutin attenuates Sorafenib-induced Chemoresistance and Autophagy in Hepatocellular Carcinoma by regulating BANCR/miRNA-590-5P/OLR1 Axis

Abstract

Rutin, the main component of Potentilla discolor Bunge, was proven to exhibit anti-tumor properties. Sorafenib (SO) is conventionally used in chemotherapy against hepatocellular carcinoma (HCC), but acquired resistance developed during long-term therapy limits its benefits. This study aimed to explore the molecular mechanism of rutin in SO-induced autophagy and chemoresistance in HCC. Sixty-eight paired HCC patients who received the same chemotherapy treatment were obtained. We also established two SO resistance cell lines and then utilized high-throughput RNA sequencing to explore their long non-coding RNA (lncRNA) expression profiles. The target microRNA (miRNA) and downstream mRNA were also explored. Our results indicated that rutin treatment attenuates autophagy and BANCR expression in SO resistance cells. Transmission electron microscopy clearly showed a significantly decreased number of autophagosomes after rutin-treated HepG2/SO and HCCLM3/SO cells. BANCR knockdown promotes the sensitivity of SO resistance cells to SO. Further study found that BANCR acts as a molecular sponge of miR-590-5P to sequester miR-590-5P away from oxidized low-density lipoprotein receptor 1 (OLR1) in HCC cells. Furthermore, in vivo study demonstrated that rutin could inhibit autophagy through the BANCR/miRNA-590-5P/OLR1 axis. Our findings suggest that rutin could regulate autophagy by regulating BANCR/miRNA-590-5P/OLR1 axis.

Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy

“…According to the results of the present experiments, the subcutaneous xenogeneic model was relatively stable ( Figure S1 ). Therefore, an implanted subcutaneous GBM was established by injecting U251 and A172 cells into Balb/c nude mice, which were then treated with 1 (low dose) or 5 (high dose) mg/kg PSPD3R every 2 days 24 to validate whether the in vitro anti-tumor effect of PSPD3R is also evident in vivo ( Figure 2 A). The xenografts in the PSPD3R-treated mice grew more slowly than those in the placebo-treated control mice.…”

Advances in Dietary Phenolic Compounds to Improve Chemosensitivity of Anticancer Drugs

“…At a dose of 20 μM, these researchers found that this flavonoid acts as a chemo-sensitizing agent by improving the anti-tumor effect of two chemotherapeutic agents (methotrexate and cyclophosphamide). Furthermore, rutin improved the in vivo efficacy of another anti-cancer drug (sorafenib) in a xenograft model of human HCC [ 42 ]. As seen with quercetin and berberine, another natural flavone called hispidulin enhanced cellular chemo-sensitivity by inhibiting the expression of the transcription factor HIF-1α via AMPK signaling in gallbladder cancer [ 43 ].…”

The MicroRNA-Based Strategies to Combat Cancer Chemoresistance via Regulating Autophagy

“…The downregulation of lncRNA MALAT1 by propofol results in inhibiting autophagy and promoting gastric cancer cells sensitive to cisplatin ( 210 ). A recent study demonstrated that rutin, the main component of Potentilla discolor Bunge, reverses sorafenib resistance by inhibiting autophagy through the BANCR/miRNA-590-5P/OLR1 axis in HCC ( 211 ). Furthermore, it is urgent to look for efficient miRNA delivery system for miRNA mimics that can’t enter cells efficiently on its own.…”