Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles

Zhao, Pengxuan; Li, Minsi; Wang, Yao; Yan, Chen; He, Chuanchuan; Zhang, Xiaojuan; Tan, Yang; Lu, Yao; You, Jia; Lee, Robert J.; Xiang, Guangya

doi:10.1016/j.actbio.2018.03.022

Cited by 71 publications

(51 citation statements)

References 36 publications

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“…chloroquine, miR-375) improves tumour response. 153,154 However, attention should be paid to the deleterious consequences of blocking autophagy in dying tumour cells, as autophagy is required for effective antitumor T cell response. Considering that immune-mediated clearance of tumour cells is crucial to suppress HCC development, a combination of immune checkpoint inhibitors together with autophagy enhancers could boost antitumor immune responses.…”

Section: Targeting Autophagy In Hepatocellular Carcinoma: a Complex Amentioning

confidence: 99%

Autophagy in liver diseases: Time for translation?

Allaire

Rautou

Codogno

et al. 2019

Journal of Hepatology

308

222

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Autophagy is a self-eating catabolic pathway that contributes to liver homeostasis through its role in energy balance and in the quality control of the cytoplasm, by removing misfolded proteins, damaged organelles and lipid droplets. Autophagy not only regulates hepatocyte functions but also impacts on non-parenchymal cells, such as endothelial cells, macrophages and hepatic stellate cells. Deregulation of autophagy has been linked to many liver diseases and its modulation is now recognized as a potential new therapeutic strategy. Indeed, enhancing autophagy may prevent the progression of a number of liver diseases, including storage disorders (alpha-1 antitrypsin deficiency, Wilson's disease), acute liver injury, non-alcoholic steatohepatitis and chronic alcohol-related liver disease. Nevertheless, in some situations such as fibrosis, targeting specific liver cells must be considered, as autophagy displays opposing functions depending on the cell type. In addition, an optimal therapeutic time-window should be identified, since autophagy might be beneficial in the initial stages of disease, but detrimental at more advanced stages, as in the case of hepatocellular carcinoma. Finally, identifying biomarkers of autophagy and methods to monitor autophagic flux in vivo are important steps for the future development of personalized autophagy-targeting strategies. In this review, we provide an update on the regulatory role of autophagy in various aspects of liver pathophysiology, describing the different strategies to manipulate autophagy and discussing the potential to modulate autophagy as a therapeutic strategy in the context of liver diseases.

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Section: Targeting Autophagy In Hepatocellular Carcinoma: a Complex Amentioning

confidence: 99%

Autophagy in liver diseases: Time for translation?

Allaire

Rautou

Codogno

et al. 2019

Journal of Hepatology

308

222

View full text Add to dashboard Cite

show abstract

“…Thus, a drug delivery system needed to facilitate the combination strategy, especially for some agents cannot enter cells efficiently by itself. By taking advantage of nanoparticles, researchers successfully coloaded miR-375, an inhibitor of autophagy and sorafenib into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs) followed by significant autophagy inhibition and enhanced antitumor effect of sorafenib in HCC (Pengxuan Zhao et al, 2018). Another group prepared R8-dGR peptide modified paclitaxel (PTX) and HCQ incorporating liposomes (PTX/HCQ -R8-dGR-Lip) for increasing drug delivery and confirmed that combined chemotherapeutic PTX with HCQ exhibited augmented efficiency on inhibiting malignant melanoma (Sheng Yin et al, 2018).…”

Section: The Challenge and Development Of Targeting Cytoprotective Aumentioning

confidence: 99%

Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy

Liu

Zhang

et al. 2020

Front. Pharmacol.

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Autophagy is considered a cytoprotective function in cancer therapy under certain conditions and is a drug resistance mechanism that represents a clinical obstacle to successful cancer treatment and leads to poor prognosis in cancer patients. Because certain clinical drugs and agents in development have cytoprotective autophagy effects, targeting autophagic pathways has emerged as a potential smarter strategy for cancer therapy. Multiple preclinical and clinical studies have demonstrated that autophagy inhibition augments the efficacy of anticancer agents in various cancers. Autophagy inhibitors, such as chloroquine and hydroxychloroquine, have already been clinically approved, promoting drug combination treatment by targeting autophagic pathways as a means of discovering and developing more novel and more effective cancer therapeutic approaches. We summarize current studies that focus on the antitumor efficiency of agents that induce cytoprotective autophagy combined with autophagy inhibitors. Furthermore, we discuss the challenge and development of targeting cytoprotective autophagy as a cancer therapeutic approach in clinical application. Thus, we need to facilitate the exploitation of appropriate autophagy inhibitors and coadministration delivery system to cooperate with anticancer drugs. This review aims to note optimal combination strategies by modulating autophagy for therapeutic advantage to overcome drug resistance and enhance the effect of antitumor therapies on cancer patients.

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“…These NPs could inhibit autophagy in HCC and produce a greater antitumor effect in a xenograft mouse model. 79 In another study, miR-375-3p was coloaded into NPs with doxorubicin (DOX), which has significant synergetic antitumor and overcoming drug resistance effects in HCC. 80 In the present study, the in vivo antitumor activity of miR-375-3p was assessed by employing the T24 subcutaneously transplanted mouse model.…”

mentioning

confidence: 99%

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

Huyan

Cai

et al. 2020

FASEB j.

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miR‐375‐3p is a significantly downregulated miRNA in bladder cancer (BC). However, its role in BC regulation is still unclear. In this study, we reported that miR‐375‐3p overexpression inhibited proliferation and migration and promoted apoptosis in BC cells. Frizzled‐8 (FZD8) gene is identified as the direct miR‐375‐3p targeting gene. miR‐375‐3p blocks the Wnt/β‐catenin pathway and downstream molecules Cyclin D1 and c‐Myc by inhibiting the expression of FZD8 directly, it could increase caspase 1 and caspase 3 expression and promote T24 cell apoptosis as well. miR‐375‐3p also showed a significant inhibitory effect in vivo in bladder tumor‐bearing nude mice, as demonstrated by the reduced tumor volume and Ki67 proliferation index in tumor tissue. Collectively, miR‐375‐3p is a suppressor of BC that inhibits proliferation and metastasis, and promotes apoptosis in BC cells as well as suppresses tumor growth in a T24 xenograft mouse model, which could be used as a potential therapeutic approach for BC in future.

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Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles

Cited by 71 publications

References 36 publications

Autophagy in liver diseases: Time for translation?

Autophagy in liver diseases: Time for translation?

Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy

The role of exosomal miR‐375‐3p: A potential suppressor in bladder cancer via the Wnt/β‐catenin pathway

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