关键词: 氧化前胡素, 乳腺癌, 多柔比星, 耐药, 甘油磷脂代谢

Abstract: AIM: To investigate the effect of oxypeucedanin (OPD) on doxorubicin resistance in human breast cancer MCF-7/DOX cells and its possible mechanism. METHODS: MCF-7/DOX cells were cultured in vitro, MTT assay was used to detect the effect of OPD on the survival of MCF-7/DOX cells, and the effect of OPD combined with different concentrations of doxorubicin on the proliferation of MCF-7/DOX cells were investigated. The effect of OPD combined with doxorubicin on the expression of genes including MDR1, MRP1, AGPAT2, CHKA, CEPT1, DGKA, PCYT1A, PLA2G15 in MCF-7/DOX cells was measured by qRT-PCR. The effect of OPD combined with doxorubicin on the protein expression of MDR1, MRP1, CHKA and CCTα in MCF-7/DOX cells was determined by Western blot. RESULTS: The IC50 value of doxorubicin in combination with OPD in MCF-7/DOX cells was lower than that of doxorubicin alone. The reversal fold is 1.56. Compared with control group, the mRNA level of MDR1, MRP1, AGPAT2, CHKA, CEPT1, DGKA, PCYT1A and PLA2G15 in the doxorubicin group was significantly downregulated (P<0.05 or P<0.01), the protein expression of MDR1, MRP1, CHKA and CCTα was not significantly affected (P>0.05), while the expression of the gene and protein above in OPD 50 μg/mL combined with doxorubicin group was significantly downregulated (P<0.05 or P<0.01). Compared with doxorubicin group, the expression of the gene above in OPD 50 μg/mL combined with doxorubicin group was further downregulated (P<0.05 or P<0.01), but the expression of the protein above was not significantly affected (P>0.05).CONCLUSION: OPD can enhance the sensitivity of MCF-7/DOX cells to doxorubicin chemotherapy, reverse drug resistance, which may be related to inhibition of glycerophospholipid metabolism.

Key words: oxypeucedanin, breast cancer, doxorubicin, drug resistance, glycerophospholipid metabolism