Co-delivery of autophagy inhibitor ATG7 siRNA and docetaxel for breast cancer treatment

Gong, Chunai; Hu, Chuling; Gu, Fenfen; Xia, Qingming; Yan, Chong; Zhang, Lijuan; Liu, Qiang; Gao, Shen; Gao, Yuan

doi:10.1016/j.jconrel.2017.09.042

Cited by 85 publications

(55 citation statements)

References 56 publications

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“…We found a central role of Atg7 for CRC cell survival. Furthermore, we could show that the protein function appears to reach beyond its very role in autophagy regulation and highlight the inhibition of Atg7 as a potential addition to standard chemotherapy regimens in CRC treatment [14].…”

Section: Introductionmentioning

confidence: 92%

Knockdown of Atg7 Induces Nuclear-LC3 Dependent Apoptosis and Augments Chemotherapy in Colorectal Cancer Cells

Scherr

Jassowicz

Pató

et al. 2020

IJMS

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Autophagy is a catabolic process that enables cells to degrade obsolete content and refuel energy depots. In colorectal cancer (CRC) autophagy has been shown to promote tumorigenesis through energy delivery in the condition of uncontrolled proliferation. With this study, we aimed at evaluating whether autophagy sustains CRC cell viability and if it impacts therapy resistance. Initially, a colorectal cancer tissue micro array, containing mucosa (n = 10), adenoma (n = 18) and adenocarcinoma (n = 49) spots, was stained for expression of essential autophagy proteins LC3b, Atg7, p62 and Beclin-1. Subsequently, central autophagy proteins were downregulated in CRC cells using siRNA technology. Viability assays, flow cytometry and immunoblotting were performed and three-dimensional cell culture was utilized to study autophagy in a tissue mimicking environment. In our study we found an upregulation of Atg7 in CRC. Furthermore, we identified Atg7 as crucial factor within the autophagy network for CRC cell viability. Its disruption induced cell death via triggering apoptosis and in combination with conventional chemotherapy it exerted synergistic effects in inducing CRC cell death. Cell death was strictly dependent on nuclear LC3b, since simultaneous knockdown of Atg7 and LC3b completely restored viability. This study unravels a novel cell death preventing function of Atg7 in interaction with LC3b, thereby unmasking a promising therapeutic target in CRC.

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Section: Introductionmentioning

confidence: 92%

Knockdown of Atg7 Induces Nuclear-LC3 Dependent Apoptosis and Augments Chemotherapy in Colorectal Cancer Cells

Scherr

Jassowicz

Pató

et al. 2020

IJMS

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“…4T1 cells were subcultured in 12-well plates at a seeding density of 2 × 10 5 per well, and the cells were further incubated for 24 h. To study the transmembrane mechanism of the DPLGA@[RAW-4T1] NPs (1 μg/ mL Dox), several specific endocytic inhibitors including chlorpromazine (30 μM, an inhibitor of clathrin),filipin (1 μg mL −1 , an inhibitor of calveoli), and amiloride (30 μM, an inhibitor of Na + /H + exchange) were used to pretreat the 4T1 cells for 1 h, as reported in our previous study [12,54]. The cells were incubated with DPLGA@ [RAW-4T1] NPs.…”

Section: Mechanism Of the Transmembranementioning

confidence: 99%

Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy

et al. 2020

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Cell membrane-covered drug-delivery nanoplatforms have been garnering attention because of their enhanced biointerfacing capabilities that originate from source cells. In this top-down technique, nanoparticles (NPs) are covered by various membrane coatings, including membranes from specialized cells or hybrid membranes that combine the capacities of different types of cell membranes. Here, hybrid membrane-coated doxorubicin (Dox)-loaded poly(lacticco-glycolic acid) (PLGA) NPs (DPLGA@[RAW-4T1] NPs) were fabricated by fusing membrane components derived from RAW264.7(RAW) and 4T1 cells (4T1). These NPs were used to treat lung metastases originating from breast cancer. This study indicates that the coupling of NPs with a hybrid membrane derived from macrophage and cancer cells has several advantages, such as the tendency to accumulate at sites of inflammation, ability to target specific metastasis, homogenous tumor targeting abilities in vitro, and markedly enhanced multi-target capability in a lung metastasis model in vivo. The DPLGA@[RAW-4T1] NPs exhibited excellent chemotherapeutic potential with approximately 88.9% anti-metastasis efficacy following treatment of breast cancer-derived lung metastases. These NPs were robust and displayed the multi-targeting abilities of hybrid membranes. This study provides a promising biomimetic nanoplatform for effective treatment of breast cancer metastasis.

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“…MCF-7 and MDA-MB-231 cells (1 × 10 6 cells/well) were seeded in six-well culture plates and allowed to attach for 24 h. Cells were treated with CBZ solution, CBZ liposomes, and CBZ NPs at 100-µM concentration for 48 h. Afterwards, incubation cells were trypsinized and centrifuged at 1000 rpm for 5 min. The extent of apoptosis was determined using the Annexin V-FITC and PI dead cell apoptosis kit (Molecular Probes, Thermo Fisher Scientific, Waltham, MA, USA) as per manufacturer’s protocol, and the treated cells were analyzed using a flow cytometer (BD FACSVerse™, Franklin Lakes, NJ, USA) [17,34].…”

Section: Methodsmentioning

confidence: 99%

Cabazitaxel-Loaded Nanocarriers for Cancer Therapy with Reduced Side Effects

et al. 2019

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Jevtana® is a micellar cabazitaxel (CBZ) solution that was approved for prostate cancer in 2010, and recently, this drug has been reported for breast cancer. The purpose of this study is to evaluate the mediated delivery of CBZ via liposomes and nanoparticles (NPs) for the treatment of breast cancer and compare these with a micellar formulation that is currently in clinical use. CBZ-loaded nanocarriers were prepared with particle sizes between 70–110 nm, and with the sustained in vitro release of CBZ for more than 28 days. Cytotoxicity studies on MCF-7 and MDA-MB-231 cells demonstrated the toxic potential of these nanocarriers. Cellular internalization revealed that NPs and liposomes have better permeability than micelles. Cell cycle analysis and apoptosis studies on MCF-7 and MDA-MB-231 cells confirmed G2/M phase arrest as well as cell death due to apoptosis and necrosis, where formulations were found to be effective compared to a micellar CBZ solution. Results from pharmacokinetic studies revealed that there is an increased circulation half-life and mean residence time for CBZ liposomes and NPs in comparison with a micellar CBZ solution. CBZ liposomes and NPs showed a reduction in hemolysis and neutropenia in comparison with a micellar CBZ solution in rats.

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Co-delivery of autophagy inhibitor ATG7 siRNA and docetaxel for breast cancer treatment

Cited by 85 publications

References 56 publications

Knockdown of Atg7 Induces Nuclear-LC3 Dependent Apoptosis and Augments Chemotherapy in Colorectal Cancer Cells

Knockdown of Atg7 Induces Nuclear-LC3 Dependent Apoptosis and Augments Chemotherapy in Colorectal Cancer Cells

Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy

Cabazitaxel-Loaded Nanocarriers for Cancer Therapy with Reduced Side Effects

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