二至丸合桂枝汤对三阴性乳腺癌细胞系顺铂耐药性的调控作用

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Abstract Objective To study the effect of Erzhi Pills and Guizhi Decoction on Cisplatin (CDDP) resistance of triple negative breast cancer (TNBC) cell lines. Methods TNBC cell line MDA-MB-231 was selected and treated with 0.01, 0.1, 0.5, 1, 5, 10 μmol/L CDDP to prepare CDDP resistant cell line (MDA-MB-231/CDDP). The cell activities of MDA-MB-231 and MDA-MB-231/CDDP were detected by CCK-8 at different concentrations (0.01, 0.1, 0.5, 1, 5, 10 μmol/L) of CDDP. At the same time, the sample wells without CDDP were used as control group. The mRNA and protein expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-lα (HIF-1α) were detected by quantitative reverse transcriptase-mediated PCR(qRT-PCR) and Western blot to verify the prepared MDA-MB-231/CDDP. MDA-MB-231/CDDP cell lines were divided into blank group (without any treatment), Erzhi Pills and Guizhi Decoction group (200 μg/ml Erzhi Pills and Guizhi Decoction), CDDP group (10 μmol/L CDDP), and combined group (200 μg/ml Erzhi Pills and Guizhi Decoction +10 μmol/L CDDP). CCK-8 and flow cytometry were used to detect cell viability and apoptosis. The mRNA and protein expressions of VEGF and HIF-1α were determined by qRT-PCR and Western blot. Results The IC50 values of MDA-MB-231 and MDA-MB-231/CDDP cells to CDDP were 1.6001 μmol/L and 36.4320 μmol/L, respectively. The mRNA expression levels of VEGF and HIF-1α in MDA-MB-231 and MDA-MB-231/CDDP cells with CDDP concentration of 10 μmol/L were lower than those in the control group, the mRNA expression level of VEGF in MDA-MB-231/CDDP cells with CDDP concentration of 10 μmol/L was higher than that in MDA-MB-231 cells, and the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01). The protein expression levels of HIF-1α and VEGF in MDA-MB-231 cells with CDDP concentration of 10 μmol/L were lower than those in the control group, and the protein expression levels of HIF-1α in MDA-MB-231/CDDP cells were lower than those in the control group, with statistical significance (P ＜ 0.05 or P ＜ 0.01). The protein expression levels of HIF-1α and VEGF in MDA-MB-231/CDDP cells with CDDP concentration of 10 μmol/L were higher than those in MDA-MB-231 cells, and the differences were statistically significant (P < 0.05). The survival rates of CDDP group and combined group 24 h after treatment were lower than those of blank group, and the cell survival rate of combined group was lower than that of CDDP group and Erzhi Pills and Guizhi Decoction group, the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01). the cell survival rate of Erzhi Pills and Guizhi Decoction group, CDDP group and combined group 48 h after treatment was lower than that of blank group, and the cell survival rate of combined group was lower than that of CDDP group and Erzhi Pills and Guizhi Decoction group, the differences were highly statistically significant (P ＜ 0.01). The apoptosis rate of Erzhi Pills and Guizhi Decoction group, CDDP group and combined group was higher than that of blank group, and the differences were highly statistically significant (P ＜ 0.01). The apoptosis rate of combined group was higher than that of Erzhi Pills and Guizhi Decoction group and CDDP group, and the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01). The mRNA and protein expression levels of HIF-1α and VEGF in MDA-MB-231/CDDP cells in CDDP group and combined group were lower than those in blank group, and those in combined group were lower than those in Erzhi Pills and Guizhi Decoction group, the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01). Conclusion Erzhi Pills and Guizhi Decoction can reverse CDDP resistance of TNBC cell line by regulating HIF-1α signaling pathway and down-regulating the VEGF expression.

Key words： Triple negative breast cancer Erzhi Pills and Guizhi Decoction Cisplatin Drug resistance

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	YANG Huifen1 MAO Juanjuan2

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YANG Huifen1 MAO Juanjuan2. Regulating effect of Erzhi Pills and Guizhi Decoction on Cisplatin resistance in triple negative breast cancer cell lines[J]. 中国医药导报, 2021, 18(25): 19-25.

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https://www.yiyaodaobao.com.cn/EN/ OR https://www.yiyaodaobao.com.cn/EN/Y2021/V18/I25/19

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