Effect and mechanism of Biyan Qingdu Granules on reversing cisplatin resistance in nasopharyngeal carcinoma cells by regulating copper ion transporter CTR1
Objective To observe the effect of Biyan Qingdu Granules on reversing cisplatin resistance in nasopharyngeal carcinoma cells,and to explore its mechanism.Methods To detect the inhibitory effect of Biyan Qingdu Granules on the proliferation of CNE-2 and CNE2/DDP cells by MTS method.To calculate the effect of Biyan Qingdu Granules on cisplatin inhibiting IC50 in CNE-2 and CNE2/DDP cells.The apoptosis of CNE2/DDP cells was determined by flow cytometry.The expressions of copper transporter and anti-apoptotic protein in CNE2/DDP cells were detected by Western Blotting.Results The cisplatin resistance index of CNE2/DDP cells was 3.03.Compared with cisplatin,the IC50 of cisplatin in CNE-2 cells of 0.1,1 and 10 mg/mL of Biyan Qingdu Granules was decreased by 12.19%,46.37%and 63.81%,respectively.Cisplatin IC50 in CNE2/DDP cells decreased by 61.75%,70.42%and 83.82%,respectively.The results of flow cytometry showed that compared with cisplatin group,CNE2/DDP in Biyan Qingdu Granules 0.1,1,10 mg/mL groups increased late apoptosis or necrosis cells(P<0.01).Western Blotting test results showed that compared with cisplatin group,the expression of copper specific transport protein(CTR1)in cisplatin+Biyan Qingdu Granules 0.1,1 and 10 mg/mL groups was significantly increased.The expressions of B-cell lymphoma 2(Bcl-2)and myeloid leukemia sequence 1(Mcl-1)were significantly decreased(P<0.05,0.01).Conclusion Biyan Qingdu Granules can enhance the cisplatin sensitivity of nasopharyngeal carcinoma cells and reverse the cisplatin resistance of CNE2/DDP cells,and its mechanism may be related to increasing the expression of CTR1 protein and decreasing the expression of Bcl-2 and Mcl-1 protein.
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