Expression of MRP and mdr1 in human gastrointestinal cancer cell lines: A correlation with resistance against doxorubicin

Murase, Masatoshi; Kodera, Yasuhiro; Kondo, Ken; Sekiguchi, Hiroyuki; Fujiwara, Michitaka; Kasai, Yasushi; Akiyama, Seiji; Ito, Katsuki

doi:10.1002/(sici)1096-9098(199603)61:3<223::aid-jso12>3.0.co;2-8

Cited by 3 publications

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References 23 publications

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“…Numerous studies have shown that inhibition of MRP1 expression by a variety of methods eased the development of drug resistance, thus supported clinical chemotherapy (20)(21)(22). Regarding the expression of MRP1 in esophageal cancer, it has been demonstrated that MRP1 often overexpressed in different esophageal cancer cell lines or cancer tissues of patients (23)(24)(25). It was even reported that the proportion of MRP1-positive samples in the esophageal cancer was significantly higher than that in the adenocarcinomas of the stomach and the colorectal adenocarcinomas, showing MRP may play a great role in the drug resistance in esophageal cancer (26).…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

et al. 2012

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Abstract. Multidrug resistance is one of the major causes limiting the efficacy of chemotherapeutic agents to control esophageal cancer. Herein, we investigated that the effect and mechanism of tetrandrine (TET) in the human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP. The human esophageal squamous carcinoma cisplatin-resistant cell line YES-2/DDP was isolated by stepwise selection in increasing concentrations of cisplatin. The CCK-8 method was carried out to measure the cell viability when cells were exposed to TET with or without cisplatin, and the IC 50 and resistance index (RI) of cisplatin was then calculated. Real-time RT-PCR and western blotting were used to detect the mRNA and protein expression of multidrug resistance 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP), respectively. Flow cytometry was adopted to determine CMFDA efflux and cell apoptosis, respectively. The resulting cell line YES-2/ DDP was 16.4-fold resistant to cisplatin, the cytotoxicity of cisplatin to YES-2/DDP cells was enhanced by TET in a dosedependent manner. Further, it was found that the expression of MDR1 and BCRP was similar in different treated cells. In contrast, the expression of MRP1 was markedly increased in YES-2/DDP cells, which was dose-dependently decreased by TET. In agreement with the results, MRP1 activity was also reversed by TET. In conclusion, TET possesses a reversal effect on drug resistance in YES-2/DDP cells through downregulation of MRP1, and has the potential to be an adjunct to chemotherapy for esophageal cancer. IntroductionChemotherapy is regarded as an important line of defense against esophageal cancer which is one of the most aggressive and lethal malignancies. However, on account of drug resistance especially multi-drug resistance (MDR), only a limited proportion of cancer patients respond favorably to commonly used chemotherapeutic drugs (1). With respect to the mechanisms of drug resistance, ATP-binding cassette (ABC) transporters, such as ABCB1/multidrug resistance 1 (MDR1), ABCC1/multidrug resistance-associated protein 1 (MRP1) and ABCG2/breast cancer resistance protein (BCRP), mediate energy-dependent drug efflux and play a main role in chemoresistance (2,3). Therefore, it seems imperative to find new drugs or methods especially targeting ABC transporters to reverse tumor drug-resistance.Tetrandrine (TET) (Fig. 1), a bis-benzylisoquinoline alkaloid isolated from the Chinese herb 'Han-Fang-Ji' (Radix Stephania tetrandra S. Moore), has been found to have immunosuppressive, free radical scavenging and anti-inflammatory activities (4-6). Furthermore, many recent studies have shown that TET exerts antitumor effects (7,8). In addition to inhibiting proliferation and inducing apoptosis of several cancer types, TET has exhibited potential as an adjunct to chemotherapy in many drug-resistant cancer cell lines (9,10). However, it remains unclear whether TET can reverse ABC transporter-mediated drug efflux. Moreover, it is als...

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Section: Discussionmentioning

confidence: 99%

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

et al. 2012

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Esophageal Cancers

Shimada¹

Human Cell Culture

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ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

Vrána

Hlaváč

Brynychová

et al. 2018

IJMS

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The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome.

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Expression of MRP and mdr1 in human gastrointestinal cancer cell lines: A correlation with resistance against doxorubicin

Cited by 3 publications

References 23 publications

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

Tetrandrine enhances cytotoxicity of cisplatin in human drug-resistant esophageal squamous carcinoma cells by inhibition of multidrug resistance-associated protein 1

Esophageal Cancers

ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

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