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| Study of reversal multidrug resistance effect of carboxymethyl chitosan on osteosarcoma MG-63/ADM cells in vitro |
| DING Wanjun1 ZENG Tao2 GUO Weichun3 YU Ling3 GE Wei1 |
1.Department of Oncology, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China;
2.Department of East Campus Endocrine, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430000, China;
3.Department of Orthopedics, Renmin Hospital of Wuhan University, Hubei Province, Wuhan 430060, China |
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Abstract Objective To observe the effect of reversing drug resistance of carboxymethyl chitosan (CMC) on human osteosarcoma resistant cell line MG-63/ADM and preliminary explore its mechanism. Methods Human osteosarcoma drug resistant MG-63/ADM cell line was cultured in vitro. The drug resistance was detected by MTT; after 24, 48 and 72 h of osteosarcoma MG-63 /ADM cells were treated with CMC + adriamycin 2.0 μg/mL, and the inhibition rate of cell proliferation in each group was measured by MTT method. The expression of P-gp in MG-63/ADM cells and the expression of NF-κB P65 protein in nucleus of MG-63/ADM cells after treated with the different concentrations of CMC were detected by Western blot. Results MTT results showed that MG-63/ADM cells were resistant to adriamycin, IC50 was (1.97±0.56) g/mL, the resistance index was 11.35; CMC could significantly inhibit MG-63/ADM cells proliferation, and the inhibitory effect was time and dose dependent (P < 0.01). Western blot test results showed that the expression of P-gp in MG-63/ADM group was significantly higher than that in MG-63 group (P < 0.05), and the expression of P-gp in MG-63/ADM treated with different concentrations of CMC was significantly lower than that in MG-63/ADM group (without drugs) (P < 0.05). The expression level of NF-κB/P65 in MG-63/ADM group was significantly higher than that in MG-63 cell group (P < 0.05). The expression of NF-κB P65 in the nucleus of CMC + ADM group was significantly lower than that of the control group (MG-63/ADM) (P < 0.05). Conclusion Carboxymethyl can partly reverse the multidrug resistance in MG-63/ADM cells, and its mechanism may be related to the inhibition of NF-κB signaling pathway and the inhibition of P-gp expression.
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