Characterisation and manipulation of docetaxel resistant prostate cancer cell lines

O’Neill, Amanda; Prencipe, Maria; Dowling, Catherine; Fan, Yue; Mulrane, Laoighse; Gallagher, William M.; O’Connor, Darran P.; O’Connor, Robert; Devery, Aoife; Corcoran, Claire; Rani, Sweta; O’Driscoll, Lorraine; Fitzpatrick, John M.; Watson, R. William G.

doi:10.1186/1476-4598-10-126

Cited by 182 publications

(193 citation statements)

References 39 publications

(46 reference statements)

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“…ABCB1 belongs to the ATP-binding cassette transporters that use the energy of ATP hydrolysis to transport substrates across cell membranes, and ABCB1 overexpression results in diminished efficacy of anticancer drugs (30). Previous studies reported that increased ABCB1 conferred resistance to chemotherapeutic agents in several cancers (31)(32)(33). ABCB1 is also closely correlated with CSC-like properties and is one of the CSC markers (23).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of ABCB1 Overcomes Cancer Stem Cell–like Properties and Acquired Resistance to MET Inhibitors in Non–Small Cell Lung Cancer

Sugano

Seike

Noro

et al. 2015

Molecular Cancer Therapeutics

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Patients with non-small cell lung cancer (NSCLC) EGFR mutations have shown a dramatic response to EGFR inhibitors (EGFR-TKI). EGFR T790M mutation and MET amplification have been recognized as major mechanisms of acquired resistance to EGFR-TKI. Therefore, MET inhibitors have recently been used in NSCLC patients in clinical trials. In this study, we tried to identify the mechanism of acquired resistance to MET inhibitors. We analyzed the antitumor effects of two MET inhibitors, PHA-665752 and crizotinib, in 10 NSCLC cell lines. EBC-1 cells with MET amplification were the only cells that were sensitive to both MET inhibitors. We established PHA-665752-resistant EBC-1 cells, namely EBC-1R cells. Activation of KRAS, EGFR, and FGFR2 signaling was observed in EBC-1R cells by FISH and receptor tyrosine kinase phosphorylation antibody arrays. EBC-1R cells also showed overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) as well as phosphorylation of MET. EBC-1R cells grew as cell spheres that exhibited cancer stem cell-like (CSC) properties and epithelial-mesenchymal transition (EMT). The level of miR-138 that targeted ABCB1 was decreased in EBC-1R cells. ABCB1 siRNA and the ABCB1 inhibitor elacridar could reduce sphere numbers and suppress EMT. Elacridar could also reverse resistance to PHA-665752 in EBC-1R cells. Our study demonstrated that ABCB1 overexpression, which was associated with CSC properties and EMT, was involved in the acquired resistance to MET inhibitors. Inhibition of ABCB1 might be a novel therapeutic strategy for NSCLC patients with acquired resistance to MET inhibitors.

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Section: Discussionmentioning

confidence: 99%

Inhibition of ABCB1 Overcomes Cancer Stem Cell–like Properties and Acquired Resistance to MET Inhibitors in Non–Small Cell Lung Cancer

Sugano

Seike

Noro

et al. 2015

Molecular Cancer Therapeutics

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“…In contrast to the increased survival observed in response to docetaxel under hyperglycaemic conditions with DU145 and LNCaP cells, we found that the response of PC3 cells to docetaxel under the same conditions was unaffected. One mechanism of resistance to docetaxel is caused by reduced drug accumulation within cells due to raised levels of proteins which promote efflux of the drug, such as the ATP-binding cassette transporter P-glycoprotein (P-gp;O'Neill et al 2011). It will be interesting to investigate whether IGFBP2 alters the sensitivity to docetaxel by affecting the levels or activity of P-gp.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2

Biernacka¹,

Uzoh²,

Zeng³

et al. 2013

Endocrine-Related Cancer

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Clinically relevant prostate cancer (PCa) is more frequent in Westernised societies and increasingly men have co-morbidities associated with a Western lifestyle, primarily diabetes, characterised by hyperinsulinaemia and hyperglycaemia. IGFs and their binding proteins (IGFBPs) are important mediators of the effects of nutrition on growth and play a key role in the development of PCa. We used DU145, PC3 and LNCaP PCa cell lines to examine how hyperglycaemia altered their response to docetaxel. Trypan Blue dye-exclusion assay was used to determine the percentage of cell death. Protein abundance was determined using western immunoblotting. Levels of IGFBP2 were measured using an ELISA. IGFBP2 gene silencing was achieved using siRNA technology. DNA methylation was assessed using combined bisulphide restriction analysis. Acetylation status of histones H3 and H4 associated with IGFBP2 gene was assessed using chromatin immunoprecipitation assay. Hyperglycaemia reduced docetaxel-induced apoptosis by 40% for DU145 cells and by 88% for LNCaP cells. This reduced cell death was mediated by a glucose-induced up-regulation of IGFBP2, as silencing IGFBP2 negated the survival effect of high glucose. Glucose increased IGFBP2 via increasing the acetylation of histones associated with the IGFBP2 gene promoter. This finding could have important implications in relation to therapeutic strategies as epigenetic modulation could be reversible.

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“…Many AMCD-resistant tumors, including docetaxel-resistant prostate cancer cells, express low levels of the proapoptotic Bax protein and high levels of the antiapoptotic BCL-2 and BCL-XL proteins, thus generating resistance to therapy-induced apoptotic cell death (O'Neill et al 2011). To date, only a few preclinical studies have explored the efficacy of antiapoptotic protein antagonists in restoring sensitivity in AMCD-resistant cancer cell lines with deregulated apoptosis.…”

Section: Mechanisms Of Acquired Resistance To Amcdsmentioning

confidence: 99%

Fighting tubulin-targeting anticancer drug toxicity and resistance

Visconti

Grieco

2017

Endocrine-Related Cancer

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Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/ slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD efficacy, reducing the acquisition of resistance by the tumor and side effects from the drug and/or its vehicle. Other possible treatments that improve outcomes in the clinic for these two drug-resistant cancers, including new formulations of the AMCDs and pursuing different molecular targets, will be discussed.

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Characterisation and manipulation of docetaxel resistant prostate cancer cell lines

Cited by 182 publications

References 39 publications

Inhibition of ABCB1 Overcomes Cancer Stem Cell–like Properties and Acquired Resistance to MET Inhibitors in Non–Small Cell Lung Cancer

Inhibition of ABCB1 Overcomes Cancer Stem Cell–like Properties and Acquired Resistance to MET Inhibitors in Non–Small Cell Lung Cancer

Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2

Fighting tubulin-targeting anticancer drug toxicity and resistance

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