Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells

// Shuqing Li 1 * , Lina Yang 1 * , Jingshu Wang 1 , Fan Liang 1 , Bin Chang 2 , Huafen Gu 1 , Honglin Wang 1 , Gong Yang 3, 4 , Yaping Chen 1 1 Department of Obstetrics and Gynecology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China 2 Department of Pathology, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 3 Cancer Institute, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 4 Central laboratory, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China * These authors have contributed equally to this work Correspondence to: Gong Yang, email: yanggong@fudan.edu.cn Yaping Chen, email: chenyaping@5thhospital.com Keywords: ovarian cancer, propadiene compound, PI3K/Akt, MAPK, ATM/Chk2 Received: April 23, 2016 Accepted: July 19, 2016 Published: August 2, 2016 ABSTRACT Epithelial ovarian cancer is most lethal in female reproductive carcinomas owing to the high chemoresistance and metastasis, so more efficient therapeutic agents are terribly needed. A propadiene compound: 1-phenylpropadienyl phosphine oxide (PHPO), was employed to test the chemotherapeutic efficacy against ovarian cancer cell lines. MTT assay showed that PHPO displayed a much lower IC50 than cisplatin and paclitaxel, while combination treatment of cells with PHPO + cisplatin induced more apoptosis than with PHPO + paclitaxel or with cisplatin + paclitaxel ( p < 0.05). Animal assays demonstrated that subcutaneous tumor growth was highly inhibited by PHPO + cisplatin, compared with that inhibited by PHPO or by cisplatin treatment alone, indicating PHPO and cisplatin may have synergistic effects against ovarian cancer growth. We also found that PHPO induced few side effects on animals, compared with cisplatin. Mechanistic studies suggested that treatment of cells with PHPO or with PHPO + cisplatin differentially inhibited the PI3K/Akt, MAPK and ATM/Chk2 pathways, which consequently suppressed the anti-apoptotic factors Bcl-xL, Bcl-2 and XIAP, but activated the pro-apoptotic factors Bad, Bax, p53, caspase 9, caspase 8, caspase 7 and PARP. Taken together, PHPO may induce cell apoptosis through multiple signal pathways, especially when used along with cisplatin. Therefore, PHPO may be explored as a prospective agent to effectively treat ovarian cancer.