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Pseudolaric Acid B Circumvents Multidrug Resistance Phenotype in Human Gastric Cancer SGC7901/ADR Cells by Downregulating Cox-2 and P-gp Expression

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Abstract

Multidrug resistance (MDR) is a challenging issue in the treatment of gastric cancer. Pseudolaric acid B is a new diterpene acid compound isolated from pseudolarix, which has been found to have anti-tumor activities in recent studies. The purpose of the present study was to evaluate the effects of pseudolaric acid B in an MDR gastric cancer cell line and elucidate the possible underlying mechanisms of action. SGC7901/ADR, a P-glycoprotein (P-gp)-overexpressing cell line, was used to evaluate the efficacy of pseudolaric acid B against MDR phenotypes. The effects of pseudolaric acid B and chemotherapeutic agents on cell proliferation and apoptosis were assessed using the MTT assay and flow cytometry, respectively. Immunocytochemistry and Western blot were used to detect the possible relevant molecules in order to elucidate the underlying mechanism of action. The results showed that pseudolaric acid B inhibited cell proliferation and induced apoptosis in SGC7901/ADR cells. A low dose of pseudolaric acid B (0.5 µmol/L) augmented the inhibitory effects of chemotherapeutic agents on proliferation (p < 0.05). The expression of P-gp and cyclooxygenase 2 (Cox-2) was downregulated with pseudolaric acid B treatment. The present results showed that pseudolaric acid B inhibited cell proliferation, induced apoptosis, circumvented MDR, and increased the sensitivity of chemotherapeutic agents in vitro by downregulating the expression of P-gp and Cox-2.

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Acknowledgments

This study was supported by a Grant of science projects from Shenyang Science and Technology Bureau (1191136-9-02). The authors would like to thank Dr. Daiming Fan, Fourth Military Medical University, Xi’an, China, for supplying SGC7901/ADR cell line.

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Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China

    Fei Yu & Suning Chen

  2. Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China

    Kai Li

  3. Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China

    Yunpeng Liu

  4. Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China

    Yan Li

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  1. Fei Yu
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  2. Kai Li
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  4. Yunpeng Liu
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  5. Yan Li
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Correspondence to Yan Li.

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Yu, F., Li, K., Chen, S. et al. Pseudolaric Acid B Circumvents Multidrug Resistance Phenotype in Human Gastric Cancer SGC7901/ADR Cells by Downregulating Cox-2 and P-gp Expression. Cell Biochem Biophys 71, 119–126 (2015). https://doi.org/10.1007/s12013-014-0170-7

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  • DOI: https://doi.org/10.1007/s12013-014-0170-7

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