Resensitization of cisplatin resistance ovarian cancer cells to cisplatin through pretreatment with low-dose fraction radiation.

Lili Zhao,Donghai Liang,Xiaoyan Yan,Hongsheng Yu,Shihai Liu,Shengnan Zhao,Wei Zhao,Tao Jiang,Yuanwei Liu

doi:10.1002/cam4.2116

Abstract

ObjectiveCisplatin is the first‐line chemotherapy for ovarian cancer. However, cisplatin resistance is severely affecting the treatment efficacy. FOXO3a has been reported to be involved in reversing chemotherapy resistance. However, whether low‐dose fraction radiation therapy (LDFRT) can reverse cisplatin resistance remains unclear. This study aimed to explore the effect of LDFRT on cisplatin resistance and its relation with FOXO3a expression in vitro.MethodsThe toxicity of cisplatin on SKOV3/DDP cells was evaluated by CCK8 assay and cell apoptosis was measured by Annexin V‐FITC staining as well as Hoechst33342 staining. The expression of FOXO3a and other relative proteins was measured by western blot.ResultsOur study found that LDFRT enhanced cisplatin‐induced apoptosis of SKOV3/DDP cells and promoted the expression of FOXO3a and pro‐apoptotic protein PUMA. In addition, overexpression of FOXO3a promoted PUMA activity and toxicity of cisplatin on SKOV3/DDP cells.ConclusionLDFRT reverses cisplatin resistance of SKOV3/DDP cells possibly by upregulating the expression of FOXO3a and its downstream target PUMA, suggesting that LDFRT might be a potent chemosensitizer for the treatment of ovarian cancer.

Highlights

Ovarian cancer is the second leading diagnosed tumor in the female reproductive tract and metastasis has been observed in 80% of patients in the first diagnosis and more than 60% of metastasis occurs in the abdominopelvic cavity with a 5‐year survival rate less than 50%
We aimed to explore the effect of low‐dose fraction radiation therapy (LDFRT) on cisplatin resistance and its relation with FOXO3a and PUMA expression in vitro
After initial treatment, cisplatin resistance is observed in some patients, which severely affects the treatment efficacy and outcome, leading to a lower 5‐year survival rate (

Summary

| INTRODUCTION

Ovarian cancer is the second leading diagnosed tumor in the female reproductive tract and metastasis has been observed in 80% of patients in the first diagnosis and more than 60% of metastasis occurs in the abdominopelvic cavity with a 5‐year survival rate less than 50%.1-3 cisplatin is beneficial in the initial treatment, after a period of time, cisplatin resistance occurs, which causes ovarian cancer recurrence and relapse in the abdominal cavity.[4]. Cisplatin is beneficial in the initial treatment, after a period of time, cisplatin resistance occurs, which causes ovarian cancer recurrence and relapse in the abdominal cavity.[4]. Identifying a new useful way to reverse cisplatin resistance during the treatment of ovarian cancer is urgently required. Clinical trials showed that LDFRT enhances the chemotherapeutic effect in human prostate cancer cells 10 and low‐dose abdominal radiation (60 cGy X 4 fractions) can act as a docetaxel chemosensitizer for recurrent ovarian cancer.[11]. Some studies found that FOXO3a plays an important role in reversing chemoresistance and inhibiting tumor proliferation and development.[13-15]. We aimed to explore the effect of LDFRT on cisplatin resistance and its relation with FOXO3a and PUMA expression in vitro PUMA, a downstream target of FOXO3a, was implicated in the radiosensitivity of tumor cells.[17,18] In this study, we aimed to explore the effect of LDFRT on cisplatin resistance and its relation with FOXO3a and PUMA expression in vitro

| MATERIALS AND METHODS

A FOXO3a

Findings

| DISCUSSION