Inhibition LC3B can increase chemosensitivity of ovarian cancer cells

Cong Qiao,Jing Tang,Jiang Zhu,Xiaobo Li,Yan He,Yuguang Ye,Xiaoming Jin,Xinxin Feng,Yanni Kan,Lei Zhang,Dan Kong,Yu Liu,Junyi Li,Dai Tang

doi:10.1186/s12935-019-0921-z

Abstract

BackgroundOvarian cancer is often accompanied by the production of ascites, and patients with repeated ascites are associated with chemotherapy resistance. The previous study confirmed that the ovarian cancer patients who developed ascites after chemotherapy had elevated autophagy levels in the ascites and precipitated cells, which was positively correlated with MDR1 expression in the blood of patients.MethodsIn order to explore the correlation between autophagy and chemoresistant, we searched TCGA and GEO database to analyze the correlation between LC3B and MDR1, and identified the targeting miRNA of LC3B. It was verified by dual luciferase that miR-204 can target LC3B. The ovarian cancer cell line and the BALB/c nude mice tumor-bearing model were selected for in vitro and in vivo verification. In vitro studies confirmed that ovarian cancer cells were more sensitive to cisplatin by inhibiting LC3B.ResultsOverexpression of miR-204 reduced the expression of LC3B, Atg7, and MDR1, and promoted apoptosis. In vivo studies have also confirmed that reducing the level of autophagy in ovarian cancer cells increases the sensitivity to cisplatin.ConclusionsIt suggests that miR-204 can be used as a tumor suppressor gene and LC3B expression level can be used as a potential molecular marker to guide the diagnosis and treatment of patients with ovarian cancer.

Highlights

Ovarian cancer is often accompanied by the production of ascites, and patients with repeated ascites are associated with chemotherapy resistance
Ovarian cancer resistance is associated with increased levels of autophagy The levels of autophagy and apoptosis markers in 116 cases of ovarian cancer ascites were detected by Enzyme‐linked immunosorbent assay (ELISA)
The results of quantitative RT-PCR (qRT-PCR) and western blot showed that compared with the sensitive group, the levels of microtubule-associated proteins 1A/1B light chain 3B (LC3B) and Beclin1 in the resistant group were significantly increased, the expression of caspase 3 and 9 was decreased, and the expression of MDR1 in the resistant group was higher than that in the sensitive group (Fig. 1b–e)

Summary

Introduction

Ovarian cancer is often accompanied by the production of ascites, and patients with repeated ascites are associated with chemotherapy resistance. The previous study confirmed that the ovarian cancer patients who developed ascites after chemotherapy had elevated autophagy levels in the ascites and precipitated cells, which was positively correlated with MDR1 expression in the blood of patients. Ovarian cancer is a platinum-sensitive disease, about 60% of patients are resistant to cisplatin and cause recurrence of the disease, often accompanied by repeated ascites [3, 4]. When tumor cells are stimulated by chemotherapeutic drugs, autophagy signaling pathway is activated, autophagy level is increased, and cell survival is promoted [8]. Inhibition of autophagy can increase the sensitivity of tumor cells to chemotherapeutic drugs [10]

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