Differentially expressed proteins in human MCF-7 breast cancer cells sensitive and resistant to paclitaxel

Pavlíková, Nela; Bartoňová, Irena; Balušíková, Kamila; Kopperová, Dana; Halada, Petr; Kovář, Jan

doi:10.1016/j.yexcr.2014.12.005

Cited by 17 publications

(21 citation statements)

References 62 publications

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“…( A ) Paclitaxel-resistant cells with high expression of ABCB1 transporter2248 were tested for their ability to accumulate KP1, KP6 and temoporfin (T). The fluorescence of PS (shown in columns) in paclitaxel-sensitive MCF-7 and paclitaxel-resistant MCF-7/PacR cells (shown in rows) was monitored by fluorescence microscopy.…”

Section: Figurementioning

confidence: 99%

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Králová

Kolář

Kahle

et al. 2017

Sci Rep

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The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design.

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Section: Figurementioning

confidence: 99%

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Králová

Kolář

Kahle

et al. 2017

Sci Rep

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“…Literature suggests, over 90% of patients of unresponsive patients have inherited or acquired resistance to the therapy 8 . Only few studies suggest a role of PI3K/Akt, FOXK2 and transgelin in paclitaxel resistance 9–13 . Due to large gaps in understanding of paclitaxel resistance mechanisms, therapeutic benefits have been limited.…”

Section: Introductionmentioning

confidence: 99%

Penfluridol overcomes paclitaxel resistance in metastatic breast cancer

Gupta

Srivastava

2019

Sci Rep

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Paclitaxel is a first line chemotherapeutic agent for the patients with metastatic breast cancer. But inherited or acquired resistance to paclitaxel leads to poor response rates in a majority of these patients. To identify mechanisms of paclitaxel resistance, we developed paclitaxel resistant breast cancer cell lines, MCF-7 and 4T1 by continuous exposure to paclitaxel for several months. Western blot analysis showed increased expression of HER2 and β-catenin pathway in resistant cell lines as compared to parent cells. Hence, we hypothesized that HER2/β-catenin mediates paclitaxel resistance in breast cancer and suppression of HER2/β-catenin signaling could overcome paclitaxel resistance. Our data showed that penfluridol (PFL) treatment significantly reduced the survival of paclitaxel-resistant cells. Western blot analysis revealed that PFL treatment suppressed HER2, as well as, β-catenin pathway. In vivo data confirmed that PFL significantly potentiated tumor growth suppressive effects of paclitaxel in an orthotropic breast cancer model. In addition, tumors from paclitaxel and PFL-treated mice showed reduced HER2 and β-catenin expression, along with increased apoptosis. Taken together our results demonstrate a novel role of HER2/β-catenin in paclitaxel resistance and open up new avenues for application of PFL as a therapeutic option for overcoming paclitaxel resistance.

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“…It is noteworthy that HSP27 suppression alone resulted in the death of prostate (Zoubeidi et al ., ) and pancreatic carcinoma cells (Baylot et al ., ). Moreover, HSP27 inhibition increases the efficacy of the chemotherapeutic agents such as gemcitabine (Baylot et al ., ), paclitaxel (Andrieu et al ., ; Pavlíková et al ., ) and doxorubicin (Díaz‐Chávez et al ., ). However, in pancreatic cancer a recent conflicting report associates an increased phosphorylation of HSP27 with better prognosis (Okuno et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Heat-shock protein 27 (HSP27, HSPB1) is synthetic lethal to cells with oncogenic activation of MET, EGFR and BRAF

et al. 2017

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The small heat‐shock protein of 27 kDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumour behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene‐addicted cancer cell lines, which undergo either cell cycle blockade or cell death in response to agents that target the specific oncogene. Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET‐addicted EBC‐1 lung cancer cells, epidermal growth factor receptor (EGFR)‐addicted colorectal carcinoma (CRC) DiFi cells and BRAF‐addicted CRC COLO205 and OXCO‐1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent. In other cell lines, such as MET‐addicted gastric carcinoma MKN45 and EGFR‐addicted CRC SW48 lines, where oncogene inhibition only blocked proliferation, HSP27 knockdown made targeted agents switch from cytostatic to cytotoxic activity. Mechanistically, the more the cells were susceptible to HSP27 suppression, the more they were primed for death, as demonstrated by increased levels of mitochondrial outer membrane permeabilization. Priming for death was accompanied by the increase in pro‐apoptotic proteins of the BCL2 family and of active caspase‐3 and lamin B. Together, these data suggest that oncogene‐addicted cells require HSP27 for survival and that HSP27 might interfere with the effectiveness of targeted agents.

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Differentially expressed proteins in human MCF-7 breast cancer cells sensitive and resistant to paclitaxel

Cited by 17 publications

References 62 publications

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms

Penfluridol overcomes paclitaxel resistance in metastatic breast cancer

Heat-shock protein 27 (HSP27, HSPB1) is synthetic lethal to cells with oncogenic activation of MET, EGFR and BRAF

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