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胡椒碱生物碱通过诱导G2/M期细胞周期阻滞、半胱天冬酶激活以及抑制细胞迁移和PI3K/Akt/GSK3β信号通路,在顺铂耐药的卵巢癌中发挥抗癌和凋亡作用。

Piperine alkaloid induces anticancer and apoptotic effects in cisplatin resistant ovarian carcinoma by inducing G2/M phase cell cycle arrest, caspase activation and inhibition of cell migration and PI3K/Akt/GSK3β signalling pathway.

作者信息

Qiu Min, Xue Chunyan, Zhang Lingyan

机构信息

Department of Obstetrics and Gynecology, Changzhou First People's Hospital, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China, 213003.

出版信息

J BUON. 2019 Nov-Dec;24(6):2316-2321.

PMID:31983100
Abstract

PURPOSE

Ovarian cancer is one the prevalent cancers in women and is responsible for 5% of all the cancer-related mortality. Owing to late diagnosis, frequent relapses, side effects of chemotherapy, development of drug resistance, there is pressing need to screen out novel and effective treatment options. Herein, we examined the anticancer effects of a secoiridoid glycoside Piperine against ovarian cancer cells.

METHODS

CCK8 assay was used to examine the anti-proliferative effects. DAPI and annexin V/propidium iodide (PI) staining assays were used to examine apoptotic cell death. Cell cycle analysis was performed by flow cytometry. The protein expressions were examined by western blotting.

RESULTS

Piperine inhibited the growth of the ovarian cancer OVACAR-3 cell with IC50 of 28 µM. In contrast, Piperine had low cytotoxic effects on the normal astrocytes (SV40) cells with an IC50 of 200 µM. Also, Piperine exerted antiproliferative effects on the OVACAR-3 ovarian cancer cells by apoptotic cell death. This was concomitant with upregulation of apoptotic proteins such as caspase 3 and 9 and Bax expressions. Piperine also induced arrest of the OVACAR-3 cells at the G2/M phase of the cell cycle. Finally, Piperine also blocked the PI3K/Akt/GSK3β signal transduction pathway in OVACAR-3 ovarian cancer cells.

CONCLUSIONS

These results suggest that Piperine exerts potent anticancer effects on ovarian cancer cells and may prove beneficial in the management of ovarian cancer.

摘要

目的

卵巢癌是女性中常见的癌症之一,占所有癌症相关死亡率的5%。由于诊断较晚、频繁复发、化疗副作用以及耐药性的产生,迫切需要筛选出新颖有效的治疗方案。在此,我们研究了一种裂环环烯醚萜苷胡椒碱对卵巢癌细胞的抗癌作用。

方法

采用CCK8法检测抗增殖作用。采用DAPI和膜联蛋白V/碘化丙啶(PI)染色法检测凋亡细胞死亡。通过流式细胞术进行细胞周期分析。通过蛋白质印迹法检测蛋白质表达。

结果

胡椒碱抑制卵巢癌OVACAR-3细胞的生长,IC50为28μM。相比之下,胡椒碱对正常星形胶质细胞(SV40)细胞的细胞毒性较低,IC50为200μM。此外,胡椒碱通过凋亡细胞死亡对OVACAR-3卵巢癌细胞发挥抗增殖作用。这伴随着凋亡蛋白如半胱天冬酶3和9以及Bax表达的上调。胡椒碱还诱导OVACAR-3细胞在细胞周期的G2/M期停滞。最后,胡椒碱还阻断了OVACAR-3卵巢癌细胞中的PI3K/Akt/GSK3β信号转导通路。

结论

这些结果表明,胡椒碱对卵巢癌细胞具有强大的抗癌作用,可能对卵巢癌的治疗有益。

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