Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters

Němcová‐Fürstová, Vlasta; Kopperová, Dana; Balušíková, Kamila; Ehrlichová, Marie; Brynychová, Veronika; Václavíková, Radka; Daniel, Petr; Souček, Pavel; Kovář, Jan

doi:10.1016/j.taap.2016.09.020

Cited by 89 publications

(86 citation statements)

References 76 publications

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“…To verify the causal link between ABCB1 overexpression and the origin of PDT resistance derived from KP1 and KP6 porphyrins, we investigated cells with acquired MDR resistance to paclitaxel strongly overexpressing ABCB12223. Paclitaxel-resistant cells MCF-7/PacR were loaded with PS and their fluorescence and phototoxicity after light exposure was evaluated and compared to parental paclitaxel-sensitive MCF-7 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Cell lines were maintained at exponential growth in RPMI 1640 medium with specific supplements used for 4T140 and for MCF-741 at 37 °C in a humidified 5% CO 2 atmosphere. Paclitaxel-resistant MCF-7 cells (MCF-7/PacR) were prepared in the laboratory of Prof. Jan Kovář (Third Faculty of Medicine, Charles University in Prague) by gradual adaptation of the original taxane-sensitive cell line to increasing paclitaxel concentration up to 300 nM paclitaxel in culture medium22. Medium supplemented with DMSO-dissolved paclitaxel (300 nM) was prepared fresh weekly.…”

Section: Methodsmentioning

confidence: 99%

“…( 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%

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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: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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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“…Accordingly, treatment with PTX might increase acquired resistance, which leads to chemotherapy failure [108]. Importantly, the mechanisms associated with the challenging and complex nature of chemoresistance [107] are still not clear [109].…”

Section: Breast Tumor Resistance To Paclitaxelmentioning

confidence: 99%

Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer

et al. 2019

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Paclitaxel (PTX), the most widely used anticancer drug, is applied for the treatment of various types of malignant diseases. Mechanisms of PTX action represent several ways in which PTX affects cellular processes resulting in programmed cell death. PTX is frequently used as the first-line treatment drug in breast cancer (BC). Unfortunately, the resistance of BC to PTX treatment is a great obstacle in clinical applications and one of the major causes of death associated with treatment failure. Factors contributing to PTX resistance, such as ABC transporters, microRNAs (miRNAs), or mutations in certain genes, along with side effects of PTX including peripheral neuropathy or hypersensitivity associated with the vehicle used to overcome its poor solubility, are responsible for intensive research concerning the use of PTX in preclinical and clinical studies. Novelties such as albumin-bound PTX (nab-PTX) demonstrate a progressive approach leading to higher efficiency and decreased risk of side effects after drug administration. Moreover, PTX nanoparticles for targeted treatment of BC promise a stable and efficient therapeutic intervention. Here, we summarize current research focused on PTX, its evaluations in preclinical research and application clinical practice as well as the perspective of the drug for future implication in BC therapy.

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“…Despite of numerous of studies detailing the characteristics of drug resistance, it still remain unsolved which justifies the complicated mechanisms. Among these mechanisms, multi-drug resistance (MDR) was drawn particular attention, which appears to be the major impediment to the success in cancer chemotherapy, due to the overexpression of ATP-binding cassette (ABC) family of drug efflux transporters, especially P-glycoprotein (P-gp; ABCB1) [6]; and drug efflux transporters was shown to be expressed in many clinical cancers, effectively excluding many clinically cancer chemotherapy drugs, including doxorubicin, vincristine, paclitaxel and etoposide, contributing to drug resistance and therapeutic failure [7][8][9]. In particular, compelling evidence has shown the correlation between the expression of ABCB1 and the chemotherapy sensitivity and survival rate of cancer patients [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

An engineered Abcb4 expressing model reveals the central role of NF-κB in the regulation of drug resistance in zebrafish

Sun

et al. 2020

Preprint

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Multidrug resistance (MDR) represents the major cause of unsatisfaction in the application of chemotherapy for cancer treatment. So far, an in vivo robust high-throughput screening system for anti-tumor drug MDR is still lacking and the molecular mechanisms for MDR still remain elusive. Given a myriad of merits of zebrafish relative to other animal models, we aimed to establish MDR system in zebrafish stably expressing ATP-binding cassette (ATP-cassette) superfamily transporters and study the potential regulatory mechanism. We first constructed a Tg(abcb4:EGFP) transgenic zebrafish stably expressing both Abcb4 and EGFP using Tol2mediated approach. The expression level of Abcb4 and EGFP was significantly induced when Tg(abcb4:EGFP) transgenic zebrafish embryos were exposed to doxorubicin (DOX) or vincristine (VCR), accompany with a marked decrease in rhodamine B (RhB) accumulation in embryos, which indicates a remarkable increase in drug efflux upon the exposure to DOX or VCR. Mechanistically, AKT and ERK signaling were activated when treated with DOX or VCR.With the application of AKT and ERK inhibitors, the drug resistance phenomena could be reversed with differential responsive effects. Of note, downstream NF-κB played a central role in the regulation of Abcb4-mediated drug resistance. Taken together, the engineered Tg(abcb4:EGFP) transgenic zebrafish model provides a new platform for drug resistance screening in vivo, which could facilitate and accelerate the process of drug development.

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Characterization of acquired paclitaxel resistance of breast cancer cells and involvement of ABC transporters

Cited by 89 publications

References 76 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

Paclitaxel’s Mechanistic and Clinical Effects on Breast Cancer

An engineered Abcb4 expressing model reveals the central role of NF-κB in the regulation of drug resistance in zebrafish

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