Inhibition of Breast Cancer Metastasis By paclitaxel-loaded pH Responsive poly(
            <i>β</i>
            -amino ester) Copolymer Micelles

Chen, Yanjun; Yue, Qiaoxin; De, Gejing; Wang, Jie; Li, Zhenzhen; Xiao, Shan; Yu, Huatao; Hai, Ma; Shi, Feng; Zhao, Qian

doi:10.2217/nnm-2016-0335

Cited by 23 publications

(23 citation statements)

References 55 publications

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“…Paclitaxel, a microtubule‐stabilizing drug is used to treat several types of cancers . It was reported that paclitaxel inhibited breast cancer metastasis . On the other hand, different administration strategies of paclitaxel induced different phenotypes of multi drug resistance in tumour cells and enhanced the metastatic capacity .…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5][6][7] It was reported that paclitaxel inhibited breast cancer metastasis. [8][9][10][11] On the other hand, different administration strategies of paclitaxel induced different phenotypes of multi drug resistance in tumour cells and enhanced the metastatic capacity. 12 Paclitaxel has been proved to reduce primary tumour volume but concurrently increased the numbers of metastatic nodules.…”

Section: Introductionmentioning

confidence: 99%

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Low doses of Paclitaxel repress breast cancer invasion through DJ‐1/KLF17 signalling pathway

Ismail

El‐Sokkary

Saber

2018

Clin Exp Pharma Physio

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Paclitaxel (taxol) is an important agent against many tumours, including breast cancer. Ample data documents that paclitaxel inhibits breast cancer metastasis while others prove that paclitaxel enhances breast cancer metastasis. The mechanisms by which paclitaxel exerts its action are not well established. This study focuses on the effect of paclitaxel, particularly the low doses on breast cancer metastasis and the mechanisms that regulate it. Current results show that, paclitaxel exerts significant cytotoxicity even at low doses in both MCF-7 and MDA-MB-231 cells. Interestingly, paclitaxel significantly inhibits cell invasion and migration, decreases Snail and increases E-cadherin mRNA expression levels at the indicated low doses. Furthermore, paclitaxel-inhibiting breast cancer metastasis is associated with down-regulation of DJ-1 and ID-1 mRNA expression level with a concurrent increase in KLF17 expression. Under the same experimental conditions, paclitaxel induces KLF17 and concurrently represses ID-1 protein levels. Our results show for the first time that paclitaxel inhibits breast cancer metastasis through regulating DJ-1/KLF17/ID-1 signalling pathway; repressed DJ-1 and ID-1 and enhanced KLF17 expression.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low doses of Paclitaxel repress breast cancer invasion through DJ‐1/KLF17 signalling pathway

Ismail

El‐Sokkary

Saber

2018

Clin Exp Pharma Physio

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“…As can be seen in Figure 5, the pH-responsive polymer prodrugs showed significant inhibitory efficacy on the growth of tumors through the enhanced cellular uptake of the drug depot by the cancer cells (Figure 1), which was consistent with our previous studies. 35 The histopathological analysis also confirmed the elevated therapeutic effect of the polymeric micelles by promoting apoptosis of CT-26 cells.…”

Section: Discussionmentioning

confidence: 59%

“…40,41 The stability of the polymer prodrugs was investigated by measurement of micelles' sizes vs incubation time according to our previous protocol. 35 As shown in Figure S5, the sizes of PELA-PBAE-ART2 prodrug showed high stability in the investigated period, whereas the sizes of other prodrugs increased to some extent during incubation. The drug grafting ratios (GR) of the polymer prodrugs were ranged from 2.14 ±1.08% to 9.57±1.24%, respectively (Table 3), which was in good agreement with the result calculated from the 1 H NMR data.…”

Section: Synthesis and Characterization Of Polymers And Polymer Prodrugsmentioning

confidence: 79%

“…The critical micelle concentration (CMC) of the polymers was determined by fluorescence measurements using pyrene fluorescence spectroscopy according to our previous report. 35 The emission wavelength was set at 390 nm with excitation slit and emission slit of 1.0 nm and 10.0 nm, respectively. The excitation intensities at a wavelength range of 300-360 nm were monitored using a fluorescence spectrophotometer (F-2000, HITACHI, Tokyo, Japan).…”

Section: Characterization Of Copolymers and Prodrugsmentioning

confidence: 99%

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<p>pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer</p>

Hao

Xie

et al. 2020

IJN

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In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(βamino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model. Methods: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core. Results: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%±1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor. Conclusion: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.

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Melatonin inhibits breast cancer cell invasion through modulating DJ‐1/KLF17/ID‐1 signaling pathway

El‐Sokkary

Ismail

Saber

2018

J of Cellular Biochemistry

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Breast cancer is the most common neoplastic disorder diagnosed in women.The main goal of this study was to explore the effect of melatonin against breast cancer metastasis and compared this with the actions of taxol (a well-known chemotherapeutic drug), and the impact of their combination against breast cancer metastasis. Melatonin showed no cytotoxic effect while taxol showed antiproliferative and cytotoxic effects on MCF-7 and MDA-MB-231 cells.Furthermore, melatonin inhibited the generation of reactive oxygen species. Melatonin and taxol clearly decreased cell migration and invasion at low doses, especially those matching the normal physiological concentration at night.Melatonin and taxol markedly reduced DJ-1 and ID-1 and increased KLF17 messenger RNA and protein expression levels. The present results also showed that melatonin and taxol induced GSK3-β nuclear and Snail cytosolic localization. These changes were accompanied by a concurrent rise in E-cadherin expression. The above data show that normal levels of melatonin may help in preventing breast cancer metastasis through inhibiting DJ-1/ KLF17/ID-1 signaling pathway. The combination of melatonin and taxol is a potent candidate against breast cancer metastasis, better than using melatonin or taxol as a single drug. K E Y W O R D S breast cancer invasion, DJ-1, KLF17, melatonin, taxol J Cell Biochem. 2019;120:3945-3957.wileyonlinelibrary.com/journal/jcb

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Inhibition of Breast Cancer Metastasis By paclitaxel-loaded pH Responsive poly( β -amino ester) Copolymer Micelles

Abstract: The pH-responsive PTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor microenvironments with improved inhibitory effects on tumor metastasis.

Cited by 23 publications

References 55 publications

Low doses of Paclitaxel repress breast cancer invasion through DJ‐1/KLF17 signalling pathway

Low doses of Paclitaxel repress breast cancer invasion through DJ‐1/KLF17 signalling pathway

<p>pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer</p>

Melatonin inhibits breast cancer cell invasion through modulating DJ‐1/KLF17/ID‐1 signaling pathway

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