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Anticancer Res. 2018 Jan;38(1):301-306.

Phenoxodiol Increases Cisplatin Sensitivity in Ovarian Clear Cancer Cells Through XIAP Down-regulation and Autophagy Inhibition.

Author information

1
Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan morikazu1118@hotmail.co.jp.
2
Department of Clinical Oncology, National Defense Medical College Hospital, Tokorozawa, Japan.
3
Department of Obstetrics and Gynecology, National Defense Medical College Hospital, Tokorozawa, Japan.

Abstract

BACKGROUND/AIM:

To investigate whether XIAP down-regulation and autophagy inhibition sensitize ovarian clear cell cancer cells to cisplatin.

MATERIALS AND METHODS:

The ovarian clear cancer cell line KK was used for in vitro analysis. Hydroxychloroquine (HCQ) and phenoxodiol (PXD) or embelin were used as autophagy and XIAP inhibitors, respectively. Non-specific and XIAP-specific siRNAs were transfected using Lipofectamine. Cytotoxicity was assessed by MTT assays. Protein expression was confirmed by western blotting.

RESULTS:

In KK, down-regulation of XIAP using specific siRNAs together with HCQ treatment enhanced the anti-tumor effect of cisplatin. Although embelin sensitized KK to cisplatin through XIAP down-regulation, it induced autophagy. However, PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition. Expression of Atg7, Atg12, and Beclin 1 was decreased after PXD treatment.

CONCLUSION:

PXD increased cisplatin sensitivity through XIAP down-regulation and autophagy inhibition and could be a new candidate for ovarian clear cell carcinoma treatment.

KEYWORDS:

Ovarian clear cell carcinoma; X-chromosome-linked inhibitor of apoptosis (XIAP); autophagy; phenoxodiol; platinum resistance

PMID:
29277787
DOI:
10.21873/anticanres.12222
[Indexed for MEDLINE]

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