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

Haixia Wang,Youjun Luo,Zhaoxia Wu,Tiankui Qiao,Zhonghua Huang

doi:10.1186/s13048-018-0468-y

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.

Highlights

Ovarian cancer is one of the most common malignant tumors of gynecology, with the highest mortality compared with other gynecologic cancer because of its acute onset, rapid progress and high metastasis rate [1, 2]
Luteolin dose dependently enhanced the proliferation inhibition effect of cisplatin in CAOV3/DDP cells Cells were treated with various doses of luteolin (0, 10, 50, and 100 μM), cisplatin (2 μg/ml) alone or in combination for 48 h and cell proliferation was monitored by Cell Counting Kit-8 (CCK-8) assay
These results suggested that luteolin enhanced the proliferation inhibition effect of cisplatin in CAOV3/DDP cells in a concentration-dependent manner

Summary

Introduction

Ovarian cancer is one of the most common malignant tumors of gynecology, with the highest mortality compared with other gynecologic cancer because of its acute onset, rapid progress and high metastasis rate [1, 2]. Epithelial ovarian cancer (EOC) accounts for 85–90% of total ovarian carcinoma and is the most aggressive one. Surgical resection combined with chemotherapy is an effective therapy method [3]. Most of the patients reach advanced stage at the time of diagnosis [4, 5]. For patients with advanced EOC, platinum-based chemotherapy is the standard of care. More than 80% of ovarian tumors response to first-line platinum-based therapy [6], the majority of patients acquire resistance to cisplatin (CDDP)

Methods

Results

Conclusion