The Journal of Membrane Biology

, Volume 248, Issue 1, pp 19–29 | Cite as

Cisplatin Activates Volume-Sensitive Like Chloride Channels Via Purinergic Receptor Pathways in Nasopharyngeal Carcinoma Cells

  • Xiaoya Yang
  • Linyan Zhu
  • Jiawei Lin
  • Shanwen Liu
  • Hai Luo
  • Jianwen Mao
  • Sihuai Nie
  • Lixin Chen
  • Liwei Wang
Article
First Online:
Received:
Accepted:

Abstract

Cisplatin-based concomitant chemoradiotherapy is considered as the standard treatment for locally advanced nasopharyngeal carcinoma patients. However, the curative efficacy of cisplatin-based chemotherapy is limited because of the occurrence of cisplatin resistance. Some researches indicate that activating the volume-sensitive Cl− channel might be a new strategy for the reduction of cisplatin resistance. However, little is known about the activation pathway of the Cl− channels activated by cisplatin. In this study, the cisplatin-activated chloride current was investigated using the whole cell patch-clamp technique in the poorly differentiated nasopharyngeal carcinoma cells (CNE-2Z cells), and the activation pathway of the current was also discussed. The results showed that extracellular application of cisplatin activated a Cl− current, showing the properties of significant outward rectification, intracellular ATP dependency, and a selectivity sequence of I− > Br− > Cl− > gluconate, and being inhibited by the Cl− channel inhibitors tamoxifen and extracellular ATP. These characteristics are similar to those of the volume-sensitive Cl− current in CNE-2Z cells, indicating that cisplatin induces the Cl− current by activating the volume-sensitive like chloride channel. The cisplatin-activated current was blocked by suramin (a wide-spectrum purinergic antagonist) and RB2 (a relatively selective P2Y antagonist). In addition, the current was depressed by extracellular application of apyrase. The apoptotic volume decrease induced by cisplatin was also attenuated by RB2. P2Y receptors were expressed in CNE-2Z cells. These results suggest that cisplatin can induce a Cl− current by activating volume-sensitive like Cl− channels through the P2Y purinoceptor pathway.

Keywords

Patch-clamp techniques Chloride channels Nasopharyngeal neoplasms Cisplatin Purinergic receptors 
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Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (81173064, 81272223, 81273539), the Natural Science Foundation (S2011010001589) and the Medical Research Foundation (B2012187) of Guangdong Province of China, the Ministry of Education of China (20124401110009), and the Science and Technology Programs in Guangzhou (2013J500015) and Dongguan (2011108102006) of China.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Xiaoya Yang
    • 1
  • Linyan Zhu
    • 2
  • Jiawei Lin
    • 2
  • Shanwen Liu
    • 2
  • Hai Luo
    • 3
  • Jianwen Mao
    • 4
  • Sihuai Nie
    • 5
  • Lixin Chen
    • 2
  • Liwei Wang
    • 3
  1. 1.Department of Physiology, College of Health SciencesGuangzhou Medical UniversityGuangzhouChina
  2. 2.Department of Pharmacology, Medical CollegeJinan UniversityGuangzhouChina
  3. 3.Department of Physiology, Medical CollegeJinan UniversityGuangzhouChina
  4. 4.Department of Biology, Guangdong Key Laboratory for Bioactive Drugs ResearchGuangdong Pharmaceutical UniversityGuangzhouChina
  5. 5.Department of PhysiologyGuangdong Medical CollegeZhanjiangChina

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