Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)

被引：33

作者：

Choi, Junjeong ^{[1
,2
]}

Lee, Ji-Hyun ^{[3
]}

Koh, Ilkyoo ^{[4
]}

Shim, Jin-Kyoung ^{[3
]}

Park, Junseong ^{[3
]}

Jeon, Jeong Yong ^{[5
]}

Yun, Mijin ^{[5
]}

Kim, Se Hoon ^{[6
]}

Yook, Jong In ^{[7
]}

Kim, Eui Hyun ^{[3
]}

Chang, Jong Hee ^{[3
]}

Kim, Sun Ho ^{[3
]}

Huh, Yong Min ^{[8
]}

Lee, Su Jae ^{[9
]}

Pollak, Michael ^{[10
]}

Kim, Pilnam ^{[4
]}

Kang, Seok-Gu ^{[3
]}

Cheong, Jae-Ho ^{[11
]}

机构：

[1] Yonsei Univ, Yonsei Inst Pharmaceut Sci, Coll Pharm, Dept Pharm, Inchon, South Korea

[2] Yonsei Univ, Brain Korea Plus Project Med Sci 21, Seoul, South Korea

[3] Yonsei Univ, Severance Hosp, Dept Neurosurg, Brain Tumor Ctr,Coll Med, Seoul, South Korea

[4] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Daejeon, South Korea

[5] Yonsei Univ, Coll Med, Severance Hosp, Dept Nucl Med, Seoul, South Korea

[6] Yonsei Univ, Coll Med, Severance Hosp, Dept Pathol, Seoul, South Korea

[7] Yonsei Univ, Coll Dent, Dept Oral Pathol, Seoul, South Korea

[8] Yonsei Univ, Coll Med, Severance Hosp, Dept Radiol, Seoul, South Korea

[9] Hanyang Univ, Res Inst Nat Sci, Dept Life Sci, Seoul, South Korea

[10] McGill Univ, Gerald Bronfman Ctr, Dept Oncol & Med, Montreal, PQ, Canada

[11] Yonsei Univ, Coll Med, Severance Hosp, Dept Surg, Seoul, South Korea

来源：

ONCOTARGET | 2016年 / 7卷 / 40期

关键词：

biguanide; glioblastoma; HL156A; invasion; stemness; tumorsphere; ADJUVANT TEMOZOLOMIDE; GLIOMA-CELLS; IN-VITRO; METFORMIN; RADIOTHERAPY; METABOLISM; PROLIFERATION; BEVACIZUMAB; CONCOMITANT; EXPRESSION;

D O I：

10.18632/oncotarget.11595

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Studies have investigated biguanide-derived agents for the treatment of cancers and have reported their effects against tumorspheres (TSs). The purpose of this study was determining the effects of HL156A, a newly designed biguanide with improved pharmacokinetics, on glioblastoma TSs (GMB TSs) and assess the feasibility of this drug as a new line of therapy against glioblastoma, alone or combined with a conventional therapeutic agent, temozolomide(TMZ). The effects of HL156A, alone and combined with TMZ, on the stemness and invasive properties of GBM TSs and survival of orthotopic xenograft animals were assessed. HL156A, combined with TMZ, inhibited the stemness of GBM TSs, proven by neurosphere formation assay and marker expression. Three-dimensional collagen matrix invasion assays provided evidence that combined treatment inhibited invasive properties, compared with control and TMZ-alone treatment groups. TMZ alone and combined treatment repressed the expression of epithelial-mesenchymal transition-related genes. A gene ontology comparison of TMZ and combination-treatment groups revealed altered expression of genes encoding proteins involved in cellular adhesion and migration. Combined treatment with HL156A and TMZ showed survival benefits in an orthotopic xenograft mouse model. The inhibitory effect of combination treatment on the stemness and invasive properties of GBM TSs suggest the potential usage of this regimen as a novel strategy for the treatment of GBM.

引用

页码：65643 / 65659

页数：17

共 43 条

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