JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE) ›› 2021, Vol. 41 ›› Issue (6): 710-716.doi: 10.3969/j.issn.1674-8115.2021.06.002

• Basic research • Previous Articles     Next Articles

Suppressing effect of the Na+/Ca2+ exchanger blocker CB-DMB on the growth of human glioblastoma cells

Jing-jing LIU(), Hui-jie HU, Zi-kai LIU, Ming-ke SONG()   

  1. Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
  • Online:2021-06-28 Published:2021-06-29
  • Contact: Ming-ke SONG;
  • Supported by:
    National Natural Science Foundation of China(81873807);Innovative Research Team of High-level Local Universities in Shanghai(SSMU-ZDCX20181201)

Abstract: Objective

·To test the inhibitory effect of the Na+/Ca2+ exchanger (NCX) blockers on the growth of human glioblastoma cells.


·Human glioblastoma cell lines (U87, U251 and SF188) and human astrocytes were cultured in vitro. The cells were treated with NCX blockers SN-6, YM244769, SEA0400, CB-DMB and the chemotherapeutic agent temozolomide (TMZ). SN-6, YM244769 and SEA0400 were selective inhibitors for the reverse operation of NCX; while CB-DMB was NCX bidirectional blocker, but preferentially blocked the forward mode of NCX. The TMZ was used as a reference drug. Cell counting kit-8 (CCK-8) assay was used to quantify and assess the cell viability, and half maximal inhibitory concentration (IC50) of the drug was obtained. Calcium imaging was used to detect the changes of Ca2+ signal in U87 cells treated with NCX inhibitors, and Western blotting was used to detect the expression of mitogen-activated protein kinase (MAPK) signaling pathway proteins. Cellular apoptosis was evaluated by flow cytometry assay.


·CCK-8 results showed that direct application of the NCX bidirectional blocker CB-DMB to glioblastoma cell lines (U87, U251 and SF188) for 48 h caused a dose-dependent growth inhibition with IC50 values of 2.06, 2.19 and 1.82 μmol/L, respectively. In contrast, NCX reverse blockers SN-6, YM244769 and SEA0400 had no significant effect on the growth activity of glioblastoma cells. CB-DMB had little effect on the growth activity of human astrocytes. Calcium imaging and Western blotting results confirmed that CB-DMB blocked the forward transport mode of NCX to elevate intracellular Ca2+, causing intracellular calcium overload and then inducing apoptosis of U87 cells and activating MAPK signaling pathway. Flow cytometry assay results showed that the rate of apoptosis induced by CB-DMB in glioblastoma cells was much faster than that induced by TMZ (P=0.002). The combination of CB-DMB and TMZ enhanced the inhibitory effect of TMZ on the growth of tumor cells.


·The inhibitory effect of CB-DMB on the growth of human glioblastoma cells may be related to blocking the forward transport mode of NCX. The plasma membrane NCX is a potential new target for the treatment of human glioblastoma.

Key words: glioblastoma, Na+/Ca2+ exchanger, blocker, CB-DMB, apoptosis, temozolomide (TMZ)

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