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Effect of dihydroartemisinin on multidrug resistance of human oral squamous cell carcinoma cell line KBV200 by regulating ROS-MAPK pathway
LIU Zu-zhi, ZHAO Yong-xing, LIN Jian-neng, ZHOU Guo-ping
2019, 28 (6):
586-590.
doi: 10.19439/j.sjos.2019.06.006
PURPOSE: To investigate the effect of dihydroartemisinin (DHA) on multidrug resistance of human oral squamous cell carcinoma cell line KBV200 and to explore its relationship with ROS-MAPK pathway. METHODS: MTT assay was used to detect the effects of different concentrations of DHA on proliferation of KB and KBV200 cells. MTT assay was used to detect the inhibition rates of cisplatin (DDP), vincristine (VCR), adriamycin (ADM), etoposide (VP-16) on proliferations of KB and KBV200 cells and the changes after DHA addition, combined with ROS inducer 3-AT, ERK inhibitor UO126, JNK inhibitor SP600125, and p38MAPK inhibitor SB203580, respectively, the difference of reversal before and after intervention was observed; the fluorescence intensity of ROS was measured by flow cytometry. SPSS 17.0 software package was used to analyze the data. RESULTS: Compared with KB cells, drug resistances of KBV200 cells to VCR, VP-16 and ADM were significantly increased(P<0.05), after 10, 20, and 30 μg/mL DHA treatment; the IC50 of KBV200 cells to VCR, VP-16 and ADM was decreased significantly in a concentration-dependent manner(P<0.05). Compared with KB cells, ROS fluorescence intensity of KBV200 cells decreased(P<0.05); after DHA treatment, ROS fluorescence intensity increased significantly, IC50 of VCR, VP-16, ADM decreased significantly(P<0.05), which was consistent with ROS promoter effect. Compared with KB cells, the levels of p-ERK/ERK, p-JNK/JNK, p-p38MAPK/p38MAPK in KBV200 cells increased significantly (P<0.05); after DHA treatment, the levels of p-ERK/ERK, p-JNK/JNK, p-p38MAPK/p38MAPK decreased significantly, IC50 of VCR, VP-16, and ADM increased significantly(P<0.05); after adding ERK inhibitor UO126, JNK inhibitor SP600125, and p38MAPK inhibitor SB203580, IC50 of VCR, VP-16, and ADM to KBV200 cells were further reduced. CONCLUSIONS: Dihydroartemisinin may reverse multidrug resistance of KBV2001 cells by promoting ROS production and inhibiting MAPK pathway.
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