HOXB4 knockdown enhances the cytotoxic effect of paclitaxel and cisplatin by downregulating ABC transporters in ovarian cancer cells

被引：19
作者：
Li, Ying [1 ]
Sun, Jingli [1 ]
Gao, Shaofeng [1 ]
Hu, Heping [2 ]
Xie, Pengmu [3 ]
机构：
[1] Shanxian Cent Hosp Shandong Prov, Dept Obstet & Gynecol, Heze 274300, Peoples R China
[2] Shanxian Cent Hosp Shandong Prov, Dept Oncol, Heze 274300, Peoples R China
[3] Jining 1 Peoples Hosp, Dept Gynaecol, 6 Jiankang Rd, Jining 272011, Peoples R China
来源：
GENE | 2018年 / 663卷
关键词：
HOXB4; Paclitaxel; Cisplatin; Ovarian cancer; ATP-binding cassette transporters; PI3K/Akt pathway; DRUG EFFLUX TRANSPORTERS; IN-VITRO CYTOTOXICITY; INCREASES EFFICACY; INHIBITION; EXPRESSION; SENSITIVITY; RESISTANCE; GENES;
D O I：
10.1016/j.gene.2018.04.033
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Therapeutic effects of anti-cancer drugs for ovarian cancer were limited due to the rapid development of chemotherapy resistance. The aim of this study was to test whether knockdown of Homeobox B4 (HOXB4) enhanced the cytotoxic effect of paclitaxel and cisplatin in ovarian cancer cells. HOXB4 expressions at mRNA and protein levels were upregulated in Taxol-resistant A2780 (A2780/Taxol) and DDP-resistant SKOV-3 (SKOV-3/DDP) cells. HOXB4 knockdown enhanced the cytotoxic effects of Taxol and DDP in A2780/Taxol and SKOV-3/DDP cells, respectively. HOXB4 silencing suppressed the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and reduced the expression of ABCB1, ABCC1 and ABCG2 in ovarian cancer cells. PI3K inhibitor LY294002 or siRNA targeting Akt (si-Akt) treatment inhibited cell viability, decreased protein levels of ABCB1, ABCC1 and ABCG2, and increased LDH release in A2780/Taxol and SKOV-3/DDP cells. These findings revealed that HOXB4 knockdown enhanced the cytotoxic effects of Taxol and DDP by downregulating ABC transporters via inhibiting the PI3K/Akt pathway in ovarian cancer cells.
引用
收藏
页码：9 / 16
页数：8
相关论文
共 27 条
[1]   Deregulated homeobox gene expression in cancer: Cause or consequence? [J].
Abate-Shen, C .
NATURE REVIEWS CANCER, 2002, 2 (10) :777-785
[2]   Ovarian cancer: Strategies for overcoming resistance to chemotherapy [J].
Agarwal, R ;
Kaye, SB .
NATURE REVIEWS CANCER, 2003, 3 (07) :502-516
[3]   Intraperitoneal cisplatin and paclitaxel in ovarian cancer [J].
Armstrong, DK ;
Bundy, B ;
Wenzel, L ;
Huang, HQ ;
Baergen, R ;
Lele, S ;
Copeland, LJ ;
Walker, JL ;
Burger, RA .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 354 (01) :34-43
[4]   The biology of ovarian cancer: new opportunities for translation [J].
Bast, Robert C., Jr. ;
Hennessy, Bryan ;
Mills, Gordon B. .
NATURE REVIEWS CANCER, 2009, 9 (06) :415-428
[5]   Functional analysis of HOXA10 and HOXB4 in human medulloblastoma cell lines [J].
Bonfim-Silva, Ricardo ;
Ferreira Melo, Fernanda Ursoli ;
Thome, Carolina Hassibe ;
Abraham, Kuruvilla Joseph ;
De Souza, Fabio Augusto Labre ;
Ramalho, Fernando Silva ;
Machado, Helio Rubens ;
De Oliveira, Ricardo Santos ;
Cardoso, Angelo A. ;
Covas, Dimas Tadeu ;
Fontes, Aparecida Maria .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2017, 51 (06) :1929-1940
[6]   Hedgehog Signaling Regulates Drug Sensitivity by Targeting ABC Transporters ABCB1 and ABCG2 in Epithelial Ovarian Cancer [J].
Chen, Yi ;
Bieber, Marcia M. ;
Teng, Nelson N. H. .
MOLECULAR CARCINOGENESIS, 2014, 53 (08) :625-634
[7]   IN-VITRO CYTOTOXICITY OF MACROMOLECULES IN DIFFERENT CELL-CULTURE SYSTEMS [J].
CHOKSAKULNIMITR, S ;
MASUDA, S ;
TOKUDA, H ;
TAKAKURA, Y ;
HASHIDA, M .
JOURNAL OF CONTROLLED RELEASE, 1995, 34 (03) :233-241
[8]  
Duan ZF, 2004, MOL CANCER THER, V3, P833
[9]   The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism [J].
Engelman, Jeffrey A. ;
Luo, Ji ;
Cantley, Lewis C. .
NATURE REVIEWS GENETICS, 2006, 7 (08) :606-619
[10]   In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. [J].
Fischer, D ;
Li, YX ;
Ahlemeyer, B ;
Krieglstein, J ;
Kissel, T .
BIOMATERIALS, 2003, 24 (07) :1121-1131
123