TanshinoneIIA enhances the chemosensitivity of breast cancer cells to doxorubicin through down-regulating the expression of MDR-related ABC transporters

Li, Kun; Lv, Hong

doi:10.1016/j.biopha.2017.10.016

Cited by 45 publications

(25 citation statements)

References 26 publications

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“…ABCG1 is a cholesterol lipid efflux pump that plays a well-known role in tumor growth, conferring chemoresistance to various malignant tumors [20]. Several ABC transporters, including ABCG1, are associated with multidrug resistance (MDR), which is a major obstacle to the effective clinical treatment of cancer [21]. In the present study, ABCG1 is a downstream protein in Wnt/ β-catenin signaling and can be significantly downregulated by Wnt/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 69%

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma

Liao

Song

et al. 2020

BMC Cancer

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Background: Chemo-resistance in hepatocellular carcinoma (HCC) is a major problem, and acquired drug resistance prevents cancer therapies from achieving complete responses. Molecular targeting therapy presents an opportunity to impede tumor through combination or sequential therapy, while the accurate effect is vague. Methods: The efficacy of combinations between oxaliplatin and anti-cancer molecular targeting drugs was screened. Strangely, the combined chemotherapy with oxaliplatin and saracatinib induced significantly antagonistic effects. Then the antitumor effects of combined treatment with saracatinib and oxaliplatin were confirmed in wide type HCC as well as in saracatinib-and oxaliplatin-resistant HCC. RNA sequencing was used to explore the resistance mechanism, and the roles of ATP-binding cassette transporter G1 (ABCG1) and Wnt signaling in oxaliplatin resistance were confirmed. Results: Chemotherapy with oxaliplatin and saracatinib individually induced strong anti-HCC effects, while combined or sequential treatment of HCC cells with these two drugs exhibited reduced efficacy compared to treatment with the single drugs. And it was saracatinib treatment caused oxaliplatin resistance. RNA sequencing revealed 458 genes that were altered by treatment with saracatinib and oxaliplatin. Of these, the gene encoding ABCG1 and Wnt-associated genes were significantly upregulated. Upregulation of ABCG1 and oxaliplatin resistance were associated with activation of Wnt signaling. Interference with ABCG1 expression or inhibition of Wnt signaling resulted in reversal of the saracatinib-induced oxaliplatin resistance in HCC. Conclusions: These studies demonstrated that combined or sequential chemotherapy with oxaliplatin and saracatinib reduced antitumor efficacy, and this antagonism was attributed to the activation of Wnt signaling and upregulation of ABCG1 by saracatinib.

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Section: Discussionmentioning

confidence: 69%

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma

Liao

Song

et al. 2020

BMC Cancer

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“…Another strategy to modulate ABC function that is being investigated in vitro and in vivo, but still not in clinical assays, is the downregulation of their expression using either small xenobiotics, natural products or small interfering RNAs (siRNAs) ( Figure 4B(d)). For instance, Tanshinon II-A from Salvia miltiorrhiza downregulated the expression of P-gp, MRP1, and BCRP in dox-resistant breast cancer cells (MCF/dox), improving Dox sensitivity [381]. Recently, it was reported that Fasudil (HA-1077), an inhibitor of Rho-associated protein kinases (ROCKs) used in China and Japan for the treatment of cerebral vasospam, increases the temozolomide (TMZ) sensitivity of TMZ-resistant gliomas in vitro and in xenografted mouse and rat by suppressing the expression of BCRP through the ROCK2/moesin/β-catenin pathway [382].…”

Section: Other Modulators Of Abc Transporter-dependent Multidrug Resimentioning

confidence: 99%

ABC Transporters at the Blood–Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas

et al. 2019

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Drug delivery into the brain is regulated by the blood–brain interfaces. The blood–brain barrier (BBB), the blood–cerebrospinal fluid barrier (BCSFB), and the blood–arachnoid barrier (BAB) regulate the exchange of substances between the blood and brain parenchyma. These selective barriers present a high impermeability to most substances, with the selective transport of nutrients and transporters preventing the entry and accumulation of possibly toxic molecules, comprising many therapeutic drugs. Transporters of the ATP-binding cassette (ABC) superfamily have an important role in drug delivery, because they extrude a broad molecular diversity of xenobiotics, including several anticancer drugs, preventing their entry into the brain. Gliomas are the most common primary tumors diagnosed in adults, which are often characterized by a poor prognosis, notably in the case of high-grade gliomas. Therapeutic treatments frequently fail due to the difficulty of delivering drugs through the brain barriers, adding to diverse mechanisms developed by the cancer, including the overexpression or expression de novo of ABC transporters in tumoral cells and/or in the endothelial cells forming the blood–brain tumor barrier (BBTB). Many models have been developed to study the phenotype, molecular characteristics, and function of the blood–brain interfaces as well as to evaluate drug permeability into the brain. These include in vitro, in vivo, and in silico models, which together can help us to better understand their implication in drug resistance and to develop new therapeutics or delivery strategies to improve the treatment of pathologies of the central nervous system (CNS). In this review, we present the principal characteristics of the blood–brain interfaces; then, we focus on the ABC transporters present on them and their implication in drug delivery; next, we present some of the most important models used for the study of drug transport; finally, we summarize the implication of ABC transporters in glioma and the BBTB in drug resistance and the strategies to improve the delivery of CNS anticancer drugs.

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“…A major cause of multidrug resistance (MDR) involves the hyperactive efflux of hydrophobic cytotoxic drugs mediated by ATP-binding cassette (ABC) proteins in mammary epithelial cells. Three commonly observed ABC proteins, which are relevant in MDR in breast cancer, include ABC transporter subfamily B member 1 or P-glycoprotein, ABCC1, and breast cancer resistance protein (or ABC subfamily G member 2) [4][5][6][7][8] . Such protein transporters function as efflux pumps for hydrophobic compounds, which intensify the transport of chemotherapeutic drugs, resulting in an ultimate reduction of the intracellular drug concentration and ineffective cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic chip enables single-cell measurement for multidrug resistance in triple-negative breast cancer cells

Parekh¹,

Noghabi²,

López³

et al. 2020

CDR

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Aims: Triple-negative breast cancer patients are commonly treated with combination chemotherapy. Nonetheless, outcomes remain substandard with relapses being of a frequent occurrence. Among the several mechanisms that result in treatment failure, multidrug resistance, which is mediated by ATP-binding cassette proteins, is the most common. Regardless of the substantial studies conducted on the heterogeneity of cancer types, only a few assays can distinguish the variability in multidrug resistance activity between individual cells. We aim to develop a single-cell assay to study this. Methods: This experiment utilized a microfluidic chip to measure the drug accumulation in single breast cancer cells in order to understand the inhibition of drug efflux properties. Results: Selection of single cells, loading of drugs, and fluorescence measurement for intracellular drug accumulation were all conducted on a microfluidic chip. As a result, measurements of the accumulation of chemotherapeutic drugs (e.g., daunorubicin and paclitaxel) in single cells in the presence and absence of cyclosporine A were conducted. Parameters such as initial drug accumulation, signal saturation time, and fold-increase of drug with and without the presence cyclosporine A were also tested. Conclusion: The results display that drug accumulation in a single-cell greatly enhanced over its same-cell control because of inhibition by cyclosporine A. Furthermore, this experiment may provide a platform for future liquid biopsy studies to characterize the multidrug resistance activity at a single-cell level.

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TanshinoneIIA enhances the chemosensitivity of breast cancer cells to doxorubicin through down-regulating the expression of MDR-related ABC transporters

Cited by 45 publications

References 26 publications

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma

Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma

ABC Transporters at the Blood–Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas

Microfluidic chip enables single-cell measurement for multidrug resistance in triple-negative breast cancer cells

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