Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion

Abstract Luteolin, a polyphenolic flavone, has been demonstrated to exert anti-tumor activity in various cancer types. Cisplatin drug resistance is a major obstacle in the management of ovarian cancer. In the present study, we investigated the chemo-sensitizing effect of luteolin in both cisplatin-r...

Full description

Bibliographic Details
Main Authors: Haixia Wang, Youjun Luo, Tiankui Qiao, Zhaoxia Wu, Zhonghua Huang
Format: Article
Language:English
Published: BMC 2018-11-01
Series:Journal of Ovarian Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13048-018-0468-y
_version_ 1797968779062280192
author Haixia Wang
Youjun Luo
Tiankui Qiao
Zhaoxia Wu
Zhonghua Huang
author_facet Haixia Wang
Youjun Luo
Tiankui Qiao
Zhaoxia Wu
Zhonghua Huang
author_sort Haixia Wang
collection DOAJ
description Abstract Luteolin, a polyphenolic flavone, has been demonstrated to exert anti-tumor activity in various cancer types. Cisplatin drug resistance is a major obstacle in the management of ovarian cancer. In the present study, we investigated the chemo-sensitizing effect of luteolin in both cisplatin-resistant ovarian cancer cell line and a mice xenotransplant model. In vitro, CCK-8 assay showed that luteolin inhibited cell proliferation in a dose-dependent manner, and luteolin enhanced anti-proliferation effect of cisplatin on cisplatin-resistant ovarian cancer CAOV3/DDP cells. Flow cytometry revealed that luteolin enhanced cell apoptosis in combination with cisplatin. Western blotting and qRT-PCR assay revealed that luteolin increased cisplatin-induced downregulation of Bcl-2 expression. In addition, wound-healing assay and Matrigel invasion assay showed that luteolin and cisplatin synergistically inhibited migration and invasion of CAOV3/DDP cells. Moreover, in vivo, luteolin enhanced cisplatin-induced reduction of tumor growth as well as induction of apoptosis. We suggest that luteolin in combination with cisplatin could potentially be used as a new regimen for the treatment of ovarian cancer.
first_indexed 2024-04-11T02:52:02Z
format Article
id doaj.art-775b2821afd143db97f506207a82ed07
institution Directory Open Access Journal
issn 1757-2215
language English
last_indexed 2024-04-11T02:52:02Z
publishDate 2018-11-01
publisher BMC
record_format Article
series Journal of Ovarian Research
spelling doaj.art-775b2821afd143db97f506207a82ed072023-01-02T16:14:25ZengBMCJournal of Ovarian Research1757-22152018-11-0111111210.1186/s13048-018-0468-yLuteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasionHaixia Wang0Youjun Luo1Tiankui Qiao2Zhaoxia Wu3Zhonghua Huang4Department of Obstetrics and Gynecology, Jinshan branch of Shanghai Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Oncology, Jinshan Hospital, Fudan UniversityDepartment of Oncology, Jinshan Hospital, Fudan UniversityDepartment of Traditional Medicine, Jinshan branch of Shanghai Sixth People’s Hospital, Shanghai Jiaotong UniversityDepartment of Obstetrics and Gynecology, Jinshan branch of Shanghai Sixth People’s Hospital, Shanghai Jiaotong UniversityAbstract Luteolin, a polyphenolic flavone, has been demonstrated to exert anti-tumor activity in various cancer types. Cisplatin drug resistance is a major obstacle in the management of ovarian cancer. In the present study, we investigated the chemo-sensitizing effect of luteolin in both cisplatin-resistant ovarian cancer cell line and a mice xenotransplant model. In vitro, CCK-8 assay showed that luteolin inhibited cell proliferation in a dose-dependent manner, and luteolin enhanced anti-proliferation effect of cisplatin on cisplatin-resistant ovarian cancer CAOV3/DDP cells. Flow cytometry revealed that luteolin enhanced cell apoptosis in combination with cisplatin. Western blotting and qRT-PCR assay revealed that luteolin increased cisplatin-induced downregulation of Bcl-2 expression. In addition, wound-healing assay and Matrigel invasion assay showed that luteolin and cisplatin synergistically inhibited migration and invasion of CAOV3/DDP cells. Moreover, in vivo, luteolin enhanced cisplatin-induced reduction of tumor growth as well as induction of apoptosis. We suggest that luteolin in combination with cisplatin could potentially be used as a new regimen for the treatment of ovarian cancer.http://link.springer.com/article/10.1186/s13048-018-0468-yLuteolinCisplatin-resistant ovarian cancerApoptosisMigrationInvasion
spellingShingle Haixia Wang
Youjun Luo
Tiankui Qiao
Zhaoxia Wu
Zhonghua Huang
Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion
Journal of Ovarian Research
Luteolin
Cisplatin-resistant ovarian cancer
Apoptosis
Migration
Invasion
title Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion
title_full Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion
title_fullStr Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion
title_full_unstemmed Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion
title_short Luteolin sensitizes the antitumor effect of cisplatin in drug-resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion
title_sort luteolin sensitizes the antitumor effect of cisplatin in drug resistant ovarian cancer via induction of apoptosis and inhibition of cell migration and invasion
topic Luteolin
Cisplatin-resistant ovarian cancer
Apoptosis
Migration
Invasion
url http://link.springer.com/article/10.1186/s13048-018-0468-y
work_keys_str_mv AT haixiawang luteolinsensitizestheantitumoreffectofcisplatinindrugresistantovariancancerviainductionofapoptosisandinhibitionofcellmigrationandinvasion
AT youjunluo luteolinsensitizestheantitumoreffectofcisplatinindrugresistantovariancancerviainductionofapoptosisandinhibitionofcellmigrationandinvasion
AT tiankuiqiao luteolinsensitizestheantitumoreffectofcisplatinindrugresistantovariancancerviainductionofapoptosisandinhibitionofcellmigrationandinvasion
AT zhaoxiawu luteolinsensitizestheantitumoreffectofcisplatinindrugresistantovariancancerviainductionofapoptosisandinhibitionofcellmigrationandinvasion
AT zhonghuahuang luteolinsensitizestheantitumoreffectofcisplatinindrugresistantovariancancerviainductionofapoptosisandinhibitionofcellmigrationandinvasion