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      The Reversal Effect and Its Mechanisms of Tetramethylpyrazine on Multidrug Resistance in Human Bladder Cancer

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      Author(s): 1 , 2 , 1 , 2 , 1 , 2 , *
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      Publication date (Electronic):
      Journal: PLoS ONE
      Publisher: Public Library of Science

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          Abstract

          Chemotherapy is an important strategy for the treatment of bladder cancer. However, the main problem limiting the success of chemotherapy is the development of multidrug resistance (MDR). To improve the management of bladder cancer, it is an urgent matter to search for strategies to reverse MDR. We chose three kinds of herbal medicines including ginsenoside Rh2, (-)-Epigallocatechin gallate (EGCG) and Tetramethylpyrazine (TMP) to detect their effects on bladder cancer. Reversal effects of these three herbal medicines for drug resistance in adriamycin (ADM)-resistant Pumc-91 cells (Pumc-91/ADM) were assessed by Cell Counting Kit-8 (CCK-8) cell proliferation assay system. The mechanisms of reversal effect for TMP were explored in Pumc-91/ADM and T24/DDP cells. After Pumc-91/ADM and T24/DDP cells were treated with TMP, cell cycle distribution analysis was performed by flow cytometry. The expression of MRP1, GST, BCL-2, LRP and TOPO-II was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), immunefluorescence assay and western blot. It was observed that TMP was capable of enhancing the cytotoxicity of anticancer agents on Pumc-91/ADM cells in response to ADM, however Rh2 and EGCG were unable to. The reversal effect of TMP was also demonstrated in T24/DDP cells. Moreover, the treatment with TMP in Pumc-91/ADM and T24/DDP cells led to an increased of G1 phase accompanied with a concomitant decrease of cell numbers in S phase. Compared to the control group, an obvious decrease of MRP1, GST, BCL-2 and an increase of TOPO-II were shown in TMP groups with a dose-dependency in mRNA and protein levels. However, there was no difference on LRP expression between TMP groups and the control group. TMP could effectively reverse MDR of Pumc-91/ADM and T24/DDP cells and its mechanisms might be correlated with the alteration of MRP1, GST, BCL-2 and TOPO-II. TMP might be a potential candidate for reversing drug resistance in bladder cancer chemotherapy.

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          Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs.

          R. Krishna, L D Mayer (2000)
          In recent years, there has been an increased understanding of P-glycoprotein (P-GP)-mediated pharmacokinetic interactions. In addition, its role in modifying the bioavailability of orally administered drugs via induction or inhibition has been also been demonstrated in various studies. This overview presents a background on some of the commonly documented mechanisms of multidrug resistance (MDR), reversal using modulators of MDR, followed by a discussion on the functional aspects of P-GP in the context of the pharmacokinetic interactions when multiple agents are coadministered. While adverse pharmacokinetic interactions have been documented with first and second generation MDR modulators, certain newer agents of the third generation class of compounds have been less susceptible in eliciting pharmacokinetic interactions. Although the review focuses on P-GP and the pharmacology of MDR reversal using MDR modulators, relevance of these drug transport proteins in the context of pharmacokinetic implications (drug absorption, distribution, clearance, and interactions) will also be discussed.
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            Bladder cancer in 2010: how far have we come?

            Bruce Jacobs, Cheryl Lee, James E Montie (2015)
            Bladder cancer is the fourth most common cancer and ranks eighth as a cause of death from cancer among men in the United States. Although guidelines assist in treatment, the art of managing bladder cancer, such as the decision to use neoadjuvant chemotherapy and the timing of cystectomy, is still variable. Bladder cancer has a propensity to recur, and with recurrence, a significant number of cases progress, which makes the early detection of high-risk patients imperative. Advances in detection, surveillance, and treatment of bladder cancer are reviewed in this article. (c) 2010 American Cancer Society, Inc.
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              Cisplatin resistance: preclinical findings and clinical implications.

              Beate Köberle, Maja Tomicic, Svetlana Usanova … (2010)
              Cisplatin is used for the treatment of many types of solid cancers. While testicular cancers respond remarkably well to cisplatin, the therapeutic efficacy of cisplatin for other solid cancers is limited because of intrinsic or acquired drug resistance. Our understanding about the mechanisms underlying cisplatin resistance has largely arisen from studies carried out with cancer cell lines in vitro. The process of cisplatin resistance appears to be multifactorial and includes changes in drug transport leading to decreased drug accumulation, increased drug detoxification, changes in DNA repair and damage bypass and/or alterations in the apoptotic cell death pathways. Translation of these preclinical findings to the clinic is emerging, but still scarce. The present review describes and discusses the clinical relevance of in vitro models by comparing the preclinical findings to data obtained in clinical studies. Copyright © 2010 Elsevier B.V. All rights reserved.
              Article 0 comments Cited 92 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Ferenc Gallyas Jr.: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 8 July 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 7
                Electronic Location Identifier: e0157759
                Affiliations
                [1 ]Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
                [2 ]Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, China
                University of Pecs Medical School, HUNGARY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MZ. Performed the experiments: SSW TL. Analyzed the data: SSW TL. Contributed reagents/materials/analysis tools: SSW TL. Wrote the paper: SSW MZ.

                Article
                Publisher ID: PONE-D-16-04994
                DOI: 10.1371/journal.pone.0157759
                PMC ID: 4938409
                PubMed ID: 27391608
                SO-VID: 4a5b6995-2fbc-44ad-b8f3-2b334a879311
                Copyright © © 2016 Wang et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 14 February 2016
                Date accepted : 3 June 2016
                Page count
                Figures: 9, Tables: 2, Pages: 19
                Funding
                Funded by: Beijing Administration of traditional Chinese medical
                Award ID: 2014-ZYJ04
                Award Recipient :
                Funded by: Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics
                Award ID: Z151100001615060
                Award Recipient :
                This study was funded by Beijing Administration of traditional Chinese medical (2014-ZYJ04) and Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics (Z151100001615060). Man Zhang received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Cancers and Neoplasms
                Subject: Genitourinary Tract Tumors
                Subject: Bladder Cancer
                Subject: Medicine and Health Sciences
                Subject: Urology
                Subject: Bladder Cancer
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Cancer Treatment
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Cancer Treatment
                Subject: Chemotherapy
                Subject: Medicine and Health Sciences
                Subject: Clinical Medicine
                Subject: Clinical Oncology
                Subject: Chemotherapy
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Clinical Oncology
                Subject: Chemotherapy
                Subject: Medicine and Health Sciences
                Subject: Pharmaceutics
                Subject: Drug Therapy
                Subject: Chemotherapy
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cell Processes
                Subject: Cell Cycle and Cell Division
                Subject: Medicine and Health Sciences
                Subject: Complementary and Alternative Medicine
                Subject: Herbal Medicine
                Subject: Medicine and Health Sciences
                Subject: Pharmacology
                Subject: Drug Interactions
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cell Processes
                Subject: Cell Cycle and Cell Division
                Subject: G1 Phase
                Subject: Biology and Life Sciences
                Subject: Molecular Biology
                Subject: Molecular Biology Techniques
                Subject: Artificial Gene Amplification and Extension
                Subject: Polymerase Chain Reaction
                Subject: Research and Analysis Methods
                Subject: Molecular Biology Techniques
                Subject: Artificial Gene Amplification and Extension
                Subject: Polymerase Chain Reaction
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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