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Food Funct. 2017 Aug 1;8(8):2857-2864. doi: 10.1039/c7fo00552k. Epub 2017 Jul 20.

Oleuropein represses the radiation resistance of ovarian cancer by inhibiting hypoxia and microRNA-299-targetted heparanase expression.

Author information

1
The Fifth Affiliated Hospital of Zunyi Medical University, ZhuHai, No. 1439 Zhufeng Road, Doumen District, Zhuhai City 519100, Guangdong Province, China. xingyubaixyb@126.com.
2
Jinzhou Medical University, No. 40 Section 3, Songpo Road, Linghe District, Jinzhou City 121000, Liaoning Province, China.
3
The First Affiliated Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang City 110001, Liaoning Province, China.
4
Cancer Hospital of China Medical University, Liaoning Cancer Hospital, No. 44 Xiaoheyan, Dadong District, Shenyang 110042, Liaoning Province, China.
5
The People's Hospital of Liaoning Province, No. 33 Wenyi Road, Shenhe District, Shenyang City 110015, Liaoning Province, China.

Abstract

Radiotherapy in ovarian cancer frequently invokes resistance; this severely compromises its therapeutic effect and results in poor clinical prognosis. How to overcome the acquired resistance and re-sensitize tumors to radiation is the central question in this clinical setting. Cancer cell survival was evaluated using a clonogenic assay. The microRNA expression profile was analyzed using a microarray. Transcript expression was determined using real time PCR. The expression of protein was determined by immunoblotting. Transcription activation was measured using a luciferase reporter assay. Transcription factor binding was determined using ChIP-PCR. Xenograft model was established and exposed to radiation with the simultaneous administration of oleuropein. Tumor growth was monitored. We demonstrated that treatment of oleuropein-sensitized ovarian cells with radiation altered the microRNA expression profile. The endogenous expression of miR-299 was suppressed by a hypoxia inducible factor and relieved in response to oleuropein, which in turn suppressed HPSE1 expression and consequently led to increased sensitivity to radiation. Our data elucidates an unappreciated mechanism mediating radiotherapy resistance in ovarian cancer and exploits the potential synergistic effect of oleuropein with radiation, which warrants further clinical investigation.

PMID:
28726915
DOI:
10.1039/c7fo00552k
[Indexed for MEDLINE]

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