Lysophosphatidic Acid Inhibits Apoptosis Induced by Cisplatin in Cervical Cancer Cells.

Yanxia Sui,Xiaoping Liu,Yi Li,Hongbing Ma,Jiansheng Wang,Xiaowei Shi,Li Tan,Shufeng Wang,Xiaozhi Zhang,Zongfang Li,Hui Cai,Yanli Yan,Ji Wang,Juan Ren,Rui Liu,Yong Zhang,Chaofan Xue,Ya Yang

doi:10.1155/2015/598386

Abstract

Cervical cancer is the second most common cause of cancer death in women worldwide. Lysophosphatidic acid (LPA) level has been found significantly increased in the serum of patients with ovarian, cervical, and colon cancers. LPA level in cervical cancer patients is significantly higher than in healthy controls. LPA receptors were found highly expressed in cervical cancer cells, suggesting LPA may play a role in the development of cervical cancer. The aim of this study is to investigate the effect of LPA on the apoptosis induced by cisplatin (DDP) in cervical cancer cell line and the underlying changes in signaling pathways. Our study found that cisplatin induced apoptosis of Hela cell through inhibiting expression of Bcl-2, upregulating the expression of Bax, Fas-L, and the enzyme activity of caspase-3 (p < 0.05); LPA significantly provided protection against the apoptosis induced by cisplatin by inhibiting the above alterations in apoptotic factor caused by cisplatin (p < 0.05). Moreover, PI3K/AKT pathway was found to be important for the LPA antiapoptosis effect, and administration of PI3K/AKT partially reversed the LPA-mediated protection against cisplatin-induced apoptosis (p < 0.05). These findings have shed new lights on the LPA bioactivity in cervical cancer cells and pointed to a possible sensitization scheme through combined administration of PI3K inhibitor and cisplatin for better treatment of cervical cancer patients, especially those with elevated LPA levels.

Highlights

Cervical cancer is the second most common type, and the second most cause of deaths, of malignancy, in females worldwide
In this study we investigate how lysophosphatidic acid (LPA)-triggered cell responses may affect the cell apoptosis induced by cisplatin in a cervical cancer cell line
Since LPA appeared to rescue Hela cells from apoptosis induced by cisplatin, we examined the LPA effect on the change of apoptosis-related proteins induced by cisplatin

Summary

Introduction

Cervical cancer is the second most common type, and the second most cause of deaths, of malignancy, in females worldwide. An estimated 500,000 new cases of cervical cancer are diagnosed, leading to 280,000 deaths, each year worldwide. The highest incidences of cervical cancers occur in developing countries. While surgery and chemoradiotherapy can cure 80%–95% of women with early stage cervical cancer, the recurrence and metastasis events are often associated with poor prognosis. High levels of lysophosphatidic acid (LPA) were firstly found in the ascites of ovarian cancers patients [1, 2]. LPA is known as an “ovarian cancer activating factor” to exert a growth factor-like effect through binding to 4 specific G protein-coupled receptors (LPA1-4). The biological activities of LPA in ovarian cancer have been studied for many years

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