Expression of multidrug-associated protein, P-glycoprotein, P53 and Bcl-2 proteins in bladder cancer and clinical implication

Chen, Z; Zhang, Y; Zhang, X; Du, Guangsheng; Yang, Weiming; Hu, Zheng; Li, J

doi:10.1007/bf02888038

Cited by 8 publications

(6 citation statements)

References 7 publications

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“…In addition, ABCB1 may also modulate the malignant properties of cancer cells (e.g., cell survival, cell proliferation, and cell invasion) independently of the transporter-mediated drug efflux [4,33] . Indeed, ABCB1 expression correlated with an advanced tumor grade or with an increasing risk of recurrence in urothelial carcinoma patients [7,9] . Therefore, it will be important to show to which extent GC treatment is associated to an increased ABCB1 expression.…”

Section: Discussionmentioning

confidence: 95%

“…However, ABCB1 may also be upregulated as part of a generalized stress response to different toxic drugs (such as gemcitabine and cisplatin), which are not ABCB1 substrates [3,4] . Expression of ABCB1 was detected in both pre-chemotherapy and post-chemotherapy tumor tissue samples from patients with bladder cancer with higher expression in post-chemotherapy patients [5–11] . Therefore, efficient second-line chemotherapies or targeted therapies for the treatment of bladder cancer need to be tested especially in a context of specific resistance mechanisms such as ABCB1 overexpression.…”

Section: Introductionmentioning

confidence: 99%

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Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics

Vallo

Michaelis

Rothweiler

et al. 2015

Translational Oncology

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Combination chemotherapy with gemcitabine and cisplatin in patients with metastatic urothelial cancer of the bladder frequently results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance could help to identify candidate treatments for an efficient second-line therapy. Six cisplatin- and six gemcitabine-resistant cell lines were established. Cell viability assays were performed to evaluate the sensitivity to 16 different chemotherapeutic substances. The activity of the drug transporter ATP-binding cassette transporter, subfamily B, member 1 (ABCB1, a critical mediator of multidrug resistance in cancer) was evaluated using fluorescent ABCB1 substrates. For functional assessment, cells overexpressing ABCB1 were generated by transduction with a lentiviral vector encoding for ABCB1, while zosuquidar was used for selective inhibition. In this study, 8 of 12 gemcitabine- or cisplatin-resistant cell lines were cross-resistant to carboplatin, 5 to pemetrexed, 4 to methotrexate, 3 to oxaliplatin, 5-fluorouracil, and paclitaxel, and 2 to cabazitaxel, larotaxel, docetaxel, topotecan, doxorubicin, and mitomycin c, and 1 of 12 cell lines was cross-resistant to vinflunine and vinblastine. In one cell line with acquired resistance to gemcitabine (TCC-SUPrGEMCI20), cross-resistance seemed to be mediated by ABCB1 expression. Our model identified the vinca alkaloids vinblastine and vinflunine, in Europe an already approved second-line therapeutic for metastatic bladder cancer, as the most effective compounds in urothelial cancer cells with acquired resistance to gemcitabine or cisplatin. These results demonstrate that this in vitro model can reproduce clinically relevant results and may be suitable to identify novel substances for the treatment of metastatic bladder cancer.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics

Vallo

Michaelis

Rothweiler

et al. 2015

Translational Oncology

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“…Furthermore, its upregulated expression is known to correlate with a poor prognosis and disease progression in varying types of cancer including ovarian and bladder (20, 21). In prostate cancer, ABCB1 has also been shown to be upregulated versus non-cancerous tissue and to positively correlate with disease stage and grade (22, 23).…”

Section: Discussionmentioning

confidence: 99%

ABCB1 Mediates Cabazitaxel–Docetaxel Cross-Resistance in Advanced Prostate Cancer

Lombard

Liu

Armstrong

et al. 2017

Molecular Cancer Therapeutics

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Advancements in research have added several new therapies for castration-resistant prostate cancer (CRPC), greatly augmenting our ability to treat patients. However, CRPC remains an incurable disease due to the development of therapeutic resistance and the existence of cross-resistance between available therapies. Understanding the interplay between different treatments will lead to improved sequencing and the creation of combinations which overcome resistance and prolong survival. Whether there exists cross-resistance between docetaxel and the next-generation taxane cabazitaxel is poorly understood. In this study, we use C4-2B and DU145 derived docetaxel-resistant cell lines to test response to cabazitaxel. Our results demonstrate that docetaxel resistance confers cross-resistance to cabazitaxel. We show that increased ABCB1 expression is responsible for cross-resistance to cabazitaxel and that inhibition of ABCB1 function through the small molecule inhibitor elacridar re-sensitizes taxane resistant cells to treatment. Additionally, the anti-androgens bicalutamide and enzalutamide, previously demonstrated to be able to re-sensitize taxane resistant cells to docetaxel through inhibition of ABCB1 ATPase activity, are also able to re-sensitize resistant cells to cabazitaxel treatment. Lastly, we show that re-sensitization using an anti-androgen is far more effective in combination with cabazitaxel than docetaxel. Collectively, these results address key concerns in the field including that of cross-resistance between taxanes and highlighting a mechanism of cabazitaxel resistance involving ABCB1. Furthermore, these preclinical studies suggest the potential in utilizing combinations of anti-androgens with cabazitaxel for increased effect in treating advanced CRPC.

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“…Conferol (38) and its oxidation productconferone (39) were extracted from dried roots of Ferula sumbul and studied as anti-HIV agents and inhibitors of cytokine release (Zhou et al 2000). Conferone (39) obtained from another species, Ferula schtschurowskiana, was determined to be a biologically active modulator of P-glycoprotein (an ABC transporter) transport (Zhong et al 2001).…”

Section: Sesquiterpene Umbelliferyl (7-hydroxycoumarin) Ethersmentioning

confidence: 99%

Sesquiterpene coumarins

Gliszczyńska

Brodelius

2011

Phytochem Rev

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Plants have a long history as therapeutic tools in the treatment of human diseases and have been used as a source of medicines for ages. In search of new biologically active natural products, many plants and herbs used in traditional medicine are screened for natural products with pharmacological activity. In this paper, we present a group of natural products, the sesquiterpene coumarins isolated from plants, and describe their wide range of biological activity. Sesquiterpene coumarins are found in some plants of the families Apiaceae (Umbelliferae), Asteraceae (Compositae) and Rutaceae. The coumarin moiety is often umbelliferone (7-hydroxycoumarin) but scopoletin (7-hydroxy-6-methoxycoumarin) and isofraxidin (7-hydroxy-6,8-dimethoxycoumarin) are also found. These coumarins are linked to a C 15 terpene moiety through an ether linkage. Another group of sesquiterpene coumarins is the prenylated 4-hydroxycoumarins where the link between the coumarin and the C 15 terpene moiety is a C-C-bond at carbon 3 of the coumarin moiety. Finally, the prenyl-furocoumarintype sesquiterpenoids are a separate group of sesquiterpene coumarins based on the suggested biosynthetic pathway. Our relatively limited knowledge on the biosynthesis of sesquiterpene coumarins is reviewed.

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Expression of multidrug-associated protein, P-glycoprotein, P53 and Bcl-2 proteins in bladder cancer and clinical implication

Cited by 8 publications

References 7 publications

Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics

Drug-Resistant Urothelial Cancer Cell Lines Display Diverse Sensitivity Profiles to Potential Second-Line Therapeutics

ABCB1 Mediates Cabazitaxel–Docetaxel Cross-Resistance in Advanced Prostate Cancer

Sesquiterpene coumarins

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