Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells.
Analysis of the chemotherapeutic effects of a propadiene compound on malignant ovarian cancer cells.
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丙二烯化合物对恶性卵巢癌细胞的化疗作用分析
DOI：
10.18632/oncotarget.11012
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发表时间：
2016-08-30
期刊：
影响因子：
--
通讯作者：
Chen Y
中科院分区：
文献类型：
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作者：
Li S;Yang L;Wang J;Liang F;Chang B;Gu H;Wang H;Yang G;Chen Y
由于高度化疗耐药和转移，上皮性卵巢癌在女性生殖系统癌症中是最致命的，因此迫切需要更有效的治疗药物。采用丙二烯化合物：1-苯基丙二烯基氧化膦（PHPO）来测试对卵巢癌细胞系的化疗效果。 MTT分析显示，PHPO的IC50远低于顺铂和紫杉醇，而PHPO+顺铂联合处理细胞比PHPO+紫杉醇或顺铂+紫杉醇联合处理细胞诱导更多的细胞凋亡(p < 0.05)。动物实验表明，与PHPO或顺铂单独治疗相比，PHPO+顺铂可高度抑制皮下肿瘤生长，表明PHPO和顺铂可能对卵巢癌生长具有协同作用。我们还发现，与顺铂相比，PHPO 对动物的副作用很少。机制研究表明，用 PHPO 或 PHPO + 顺铂处理细胞会差异性地抑制 PI3K/Akt、MAPK 和 ATM/Chk2 通路，从而抑制抗凋亡因子 Bcl-xL、Bcl-2 和 XIAP，但激活促凋亡因子 Bad、Bax、p53、caspase 9、caspase 8、caspase 7 和 PARP。综上所述，PHPO 可能通过多种信号途径诱导细胞凋亡，特别是与顺铂一起使用时。因此，PHPO可能被探索作为有效治疗卵巢癌的前瞻性药物。
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.