title: Lysophosphatidic Acid Inhibits Apoptosis Induced by Cisplatin in Cervical Cancer Cells.
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.
authors.affiliation: Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China ; Pathology Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.affiliation: ICU, China Meitan General Hospital, 29 Xi Ba He Nan Li, Chaoyang District, Beijing 100028, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Chemotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Anesthesia, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Xi'an Children Hospital, Xi'an, Shaanxi 710000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Oncology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Xiaozhi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Chaofan
authors.initials: C
authors.lastname: Xue
authors.affiliation: Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Shi
authors.affiliation: Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Radiotherapy Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Ren
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008246:Lysophospholipids; D051025:bcl-Associated Death Protein; D019014:fas Receptor; D019869:Phosphatidylinositol 3-Kinases; D053148:Caspase 3; C032881:lysophosphatidic acid; D002945:Cisplatin