FTY720 enhances the anti-tumor activity of carboplatin and tamoxifen in a patient-derived xenograft model of ovarian cancer.
FTY720 enhances the anti-tumor activity of carboplatin and tamoxifen in a patient-derived xenograft model of ovarian cancer.
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DOI：
10.1016/j.canlet.2018.08.015
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发表时间：
2018-11-01
期刊：
影响因子：
9.7
通讯作者：
Yoon KJ
中科院分区：
文献类型：
--
作者：
Kreitzburg KM;Fehling SC;Landen CN;Gamblin TL;Vance RB;Arend RC;Katre AA;Oliver PG;van Waardenburg RCAM;Alvarez RD;Yoon KJ
卵巢癌是美国女性癌症相关死亡的第五大原因。尽管大多数患者对一线治疗有反应，但几乎所有患者都会出现耐药性疾病复发。这项研究提出了这样的假设：卡铂或他莫昔芬 + FTY720（一种鞘氨醇类似物）将最大限度地减少或避免卵巢癌细胞和肿瘤模型中的耐药性。体外数据表明，FTY720 使两种耐药细胞系（A2780.cp20、HeyA8.MDR）和两种高级浆液性卵巢癌细胞系（COV362、CAOV3）对卡铂（卵巢癌患者的护理标准）和选择性雌激素受体调节剂他莫昔芬敏感。 FTY720 + 他莫昔芬在体外具有协同作用，并且在患者来源的卵巢癌异种移植模型中，FTY720 + 卡铂或 + 他莫昔芬的组合比每种单一药物更有效。 FTY720 + 他莫昔芬抑制肿瘤生长。 FTY720 + 卡铂诱导肿瘤消退，与初始肿瘤体积相比，肿瘤体积减少约 86%。抗肿瘤功效伴随着细胞内促凋亡脂质神经酰胺的增加。数据表明FTY720+他莫昔芬或卡铂可能有效治疗卵巢肿瘤。
Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. Although most patients respond to frontline therapy, virtually all patients relapse with chemoresistant disease. This study addresses the hypothesis that carboplatin or tamoxifen + FTY720, a sphingosine analogue, will minimize or circumvent drug-resistance in ovarian cancer cells and tumor models. In vitro data demonstrate that FTY720 sensitized two drug-resistant (A2780.cp20, HeyA8.MDR) and two high-grade serous ovarian cancer cell lines (COV362, CAOV3) to carboplatin, a standard of care for patients with ovarian cancer, and to the selective estrogen receptor modulator tamoxifen. FTY720 + tamoxifen was synergistic in vitro, and combinations of FTY720 + carboplatin or + tamoxifen were more effective than each single agent in a patient-derived xenograft model of ovarian carcinoma. FTY720 + tamoxifen arrested tumor growth. FTY720 + carboplatin induced tumor regressions, with tumor volumes reduced by ~86% compared to initial tumor volumes. Anti-tumor efficacy was concomitant with increases in intracellular proapoptotic lipid ceramide. The data suggest that FTY720 + tamoxifen or carboplatin may be effective in treating ovarian tumors.
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DOI：
10.1038/nrc4019
发表时间：
2015-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Bowtell DD;Böhm S;Ahmed AA;Aspuria PJ;Bast RC Jr;Beral V;Berek JS;Birrer MJ;Blagden S;Bookman MA;Brenton JD;Chiappinelli KB;Martins FC;Coukos G;Drapkin R;Edmondson R;Fotopoulou C;Gabra H;Galon J;Gourley C;Heong V;Huntsman DG;Iwanicki M;Karlan BY;Kaye A;Lengyel E;Levine DA;Lu KH;McNeish IA;Menon U;Narod SA;Nelson BH;Nephew KP;Pharoah P;Powell DJ Jr;Ramos P;Romero IL;Scott CL;Sood AK;Stronach EA;Balkwill FR
通讯作者：
Balkwill FR
影响因子：
5.8
作者：
Morad, Samy A. F.;Madigan, James P.;Levin, Jonathan C.;Abdelmageed, Noha;Karimi, Ramin;Rosenberg, Daniel W.;Kester, Mark;Shanmugavelandy, Sriram S.;Cabot, Myles C.
通讯作者：
Cabot, Myles C.
影响因子：
11.5
作者：
Devalapally, Harikrishna;Duan, Zhenfeng;Amiji, Mansoor M.
通讯作者：
Amiji, Mansoor M.
影响因子：
5.7
作者：
Guillermet-Guibert, Julie;Davenne, Lise;Bousquet, Corinne
通讯作者：
Bousquet, Corinne
SET介导的NDRG1抑制参与人肺癌细胞上皮间质转化表型的获得和顺铂耐药
影响因子：
4.8
作者：
Liu, Hao;Gu, Yixue;He, Zhimin
通讯作者：
He, Zhimin