Roles of volume-sensitive Cl- channel in cisplatin resistance of human lung adenocarcinoma cells

X. Min, H. Li, J. Liu, J. Wang (Beijing, China)

Source: Annual Congress 2010 - Pathology of lung cancer
Session: Pathology of lung cancer
Session type: Thematic Poster Session
Number: 3272

Congress or journal article abstract

Abstract

The apoptotic volume decrease (AVD) is an early prerequisite to apoptotic events leading to cell death. We have demonstrated that AVD was associated with activity of the volume sensitive outwardly rectifying (VSOR) Cl- channel, which is essential to the progression of apoptosis in our previous research. The present study was designed to find out whether VSOR Cl- channel is involved in cisplatin II [cis-diaminodichloroplatinum, CDDP]-induced AVD process and cisplatin resistance of the human lung adenocarcinoma cell. The AVD process was measured in A549 cells, which serve as a model of sensitive to cisplatin and A549/CDDP cells, which serve as a model of cisplatin resistance. Whole-cell patch clamp was occupied to record VSOR Cl- currents induced by hypotonicity. The results showed that CDDP pretreatment induced AVD process in A549 cells but not in A549/CDDP cells. The VSOR Cl- currents were nearly absent in A549/CDDP cells compared with the parallel A549 cells. And the relative cell viability of A549/CDDP cells was much higher than A549 after treated with CDDP. Pretreatment the cells a histone deacetylase inhibitor, trichostatin A (TSA), not only partially restored VSOR Cl- channel activity, but also decreased the cell viability of A549/CDDP cells treated with CDDP. These results indicate that impaired activity of VSOR Cl- channel is involved in cisplatin resistance of human lung adenocarcinoma cells and restoration of the functional expression of the VSOR Cl- channel would lead to a increase in the sensitivity of cisplatin.


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Citations should be made in the following way:
X. Min, H. Li, J. Liu, J. Wang (Beijing, China). Roles of volume-sensitive Cl- channel in cisplatin resistance of human lung adenocarcinoma cells. Eur Respir J 2010; 36: Suppl. 54, 3272

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