The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes.
The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes.
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DOI：
10.3390/ijms23010073
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发表时间：
2021-12-22
影响因子：
5.6
通讯作者：
Vaclavikova R
中科院分区：
文献类型：
--
作者：
Seborova K;Kloudova-Spalenkova A;Koucka K;Holy P;Ehrlichova M;Wang C;Ojima I;Voleska I;Daniel P;Balusikova K;Jelinek M;Kovar J;Rob L;Hruda M;Mrhalova M;Soucek P;Vaclavikova R
阻碍常规紫杉烷类药物治疗成功的主要问题是紫杉烷类药物的新生耐药或获得性耐药。因此，新的实验紫杉烷衍生物（斯托尼布鲁克紫杉烷; SB-Ts）的合成和测试作为潜在的药物对耐药的实体瘤。最近，我们报道了ABCC 3，CPS 1和TRIP 6基因表达在乳腺癌细胞株耐紫杉醇的改变。本研究旨在研究这三种候选分子在体外高耐药卵巢癌细胞和相应的体内模型中的基因表达变化，这些细胞经紫杉醇和新的实验性第三代斯托尼布鲁克紫杉烷（SB-T-121605和SB-T-121606）处理。我们还讨论了它们在紫杉烷类药物治疗的卵巢癌患者中的预后意义。我们在体外和体内评估和观察了耐药和敏感卵巢癌细胞以及紫杉醇和斯托尼布鲁克紫杉烷治疗耐药卵巢癌模型后ABCC 3、CPS 1和TRIP 6的mRNA和蛋白质谱的变化。联合使用斯托尼布鲁克紫杉烷类和紫杉醇导致体内紫杉醇耐药小鼠异种移植肿瘤模型中CPS 1下调。此外，CPS 1过表达似乎是上皮性卵巢癌患者生存不良的预后生物标志物。ABCC 3在EOC肿瘤中过表达，但在紫杉烷类药物治疗后，其上调消失。基于我们的结果，我们可以建议ABCC 3和CPS 1作为人类癌症的潜在治疗靶点进行进一步研究。
The main problem precluding successful therapy with conventional taxanes is de novo or acquired resistance to taxanes. Therefore, novel experimental taxane derivatives (Stony Brook taxanes; SB-Ts) are synthesized and tested as potential drugs against resistant solid tumors. Recently, we reported alterations in ABCC3, CPS1, and TRIP6 gene expression in a breast cancer cell line resistant to paclitaxel. The present study aimed to investigate gene expression changes of these three candidate molecules in the highly resistant ovarian carcinoma cells in vitro and corresponding in vivo models treated with paclitaxel and new experimental Stony Brook taxanes of the third generation (SB-T-121605 and SB-T-121606). We also addressed their prognostic meaning in ovarian carcinoma patients treated with taxanes. We estimated and observed changes in mRNA and protein profiles of ABCC3, CPS1, and TRIP6 in resistant and sensitive ovarian cancer cells and after the treatment of resistant ovarian cancer models with paclitaxel and Stony Brook taxanes in vitro and in vivo. Combining Stony Brook taxanes with paclitaxel caused downregulation of CPS1 in the paclitaxel-resistant mouse xenograft tumor model in vivo. Moreover, CPS1 overexpression seems to play a role of a prognostic biomarker of epithelial ovarian carcinoma patients’ poor survival. ABCC3 was overexpressed in EOC tumors, but after the treatment with taxanes, its up-regulation disappeared. Based on our results, we can suggest ABCC3 and CPS1 for further investigations as potential therapeutic targets in human cancers.
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影响因子：
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作者：
Hansen, Stine Ninel;Westergaard, David;Schrohl, Anne-Sofie
通讯作者：
Schrohl, Anne-Sofie
影响因子：
--
作者：
Adamska, Aleksandra;Ferro, Riccardo;Falasca, Marco
通讯作者：
Falasca, Marco
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
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.6
作者：
Ehrlichova, M;Vaclavikova, R;Gut, I
通讯作者：
Gut, I