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胡椒碱作用于人类卵巢癌细胞系的不同耐药机制,导致对细胞毒性药物的敏感性增加。

Piperine Targets Different Drug Resistance Mechanisms in Human Ovarian Cancer Cell Lines Leading to Increased Sensitivity to Cytotoxic Drugs.

作者信息

Wojtowicz Karolina, Sterzyńska Karolina, Świerczewska Monika, Nowicki Michał, Zabel Maciej, Januchowski Radosław

机构信息

Department of Histology and Embryology, Poznań University of Medical Sciences, Święcickiego 6 St., 61-781 Poznań, Poland.

Department of Anatomy and Histology, Collegium Medicum, University of Zielona Gora, Zyty 28 St., 65-046 Zielona Gora, Poland.

出版信息

Int J Mol Sci. 2021 Apr 19;22(8):4243. doi: 10.3390/ijms22084243.

DOI:10.3390/ijms22084243
PMID:33921897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8073496/
Abstract

Our goal was to examine the anticancer effects of piperine against the resistant human ovarian cancer cells and to explore the molecular mechanisms responsible for its anticancer effects. Our study used drug-sensitive ovarian cancer cell line W1 and its sublines resistant to paclitaxel (PAC) and topotecan (TOP). We analyzed the cytotoxic effect of piperine and cytostatic drugs using an MTT assay. The impact of piperine on protein expression was determined by immunofluorescence and Western blot. We also examined its effect on cell proliferation and migration. We noticed a different level of piperine resistance between cell lines. Piperine increases the cytotoxic effect of PAC and TOP in drug-resistant cells. We observed an increase in PTPRK expression correlated with decreased pTYR level after piperine treatment and downregulation of P-gp and BCRP expression. We also noted a decrease in COL3A1 and TGFBI expression in investigated cell lines and increased COL3A1 expression in media from W1PR2 cells. The expression of Ki67 protein and cell proliferation rate decreased after piperine treatment. Piperine markedly inhibited W1TR cell migration. Piperine can be considered a potential anticancer agent that can increase chemotherapy effectiveness in cancer patients.

摘要

我们的目标是研究胡椒碱对耐药性人卵巢癌细胞的抗癌作用,并探索其抗癌作用的分子机制。我们的研究使用了对药物敏感的卵巢癌细胞系W1及其对紫杉醇(PAC)和拓扑替康(TOP)耐药的亚系。我们使用MTT法分析了胡椒碱和细胞生长抑制剂的细胞毒性作用。通过免疫荧光和蛋白质印迹法测定胡椒碱对蛋白质表达的影响。我们还研究了其对细胞增殖和迁移的影响。我们注意到细胞系之间胡椒碱耐药水平存在差异。胡椒碱增加了耐药细胞中PAC和TOP的细胞毒性作用。我们观察到胡椒碱处理后PTPRK表达增加,同时pTYR水平降低,P-糖蛋白和乳腺癌耐药蛋白(BCRP)表达下调。我们还注意到在所研究的细胞系中COL3A1和TGFBI表达降低,而W1PR2细胞培养基中COL3A1表达增加。胡椒碱处理后Ki67蛋白表达和细胞增殖率降低。胡椒碱显著抑制W1TR细胞迁移。胡椒碱可被视为一种潜在的抗癌药物,能够提高癌症患者化疗的有效性。

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