Analysis of anticancer drug-resistant ovarian cancer cells under hypoxic tumor microenvironment

缺氧肿瘤微环境下卵巢癌细胞抗癌耐药性分析

• 批准号: 21890130
• 负责人: HAYASHI Masami
• 金额: $ 1.66万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21890130/
• 关键词: 卵巣癌; 抗癌剤耐性; Akt; mTOR

Paclitaxel-resistant ovarian cancer cells showed the activation of Akt and significantly higher levels of Akt2 expression compared with paclitaxel-sensitive cells. An HIF-2α expression was also higher in paclitaxel-resistant cells than in paclitaxel-sensitive cells.We next examined the significance of Akt2 in paclitaxel-resistant in vivo tumor growth by selectively inhibiting Akt2. An siRNA targeting Akt2 inhibited ovarian tumor growth in nude mice. These results indicated molecular target treatment against either Akt2 or HIF-2α would be useful for the paclitaxel-resistant ovarian cancer.

紫杉醇耐药卵巢癌细胞显示Akt的激活和显着较高水平的Akt 2表达与紫杉醇敏感细胞相比。HIF-2α在紫杉醇耐药细胞中的表达也高于紫杉醇敏感细胞。我们接下来通过选择性抑制Akt 2来检测Akt 2在紫杉醇耐药体内肿瘤生长中的意义。靶向Akt 2的siRNA抑制裸鼠卵巢肿瘤生长。这些结果表明，针对Akt 2或HIF-2α的分子靶向治疗对于紫杉醇耐药的卵巢癌是有用的。

项目成果

Vascular endothelial growth factor is a promising therapeutic target for the treatment of clear cell carcinoma of the ovary.

• DOI: 10.1158/1535-7163.mct-10-0169
• 发表时间: 2010-08
• 期刊: Molecular cancer therapeutics
• 影响因子: 5.7
• 作者: Mabuchi S;Kawase C;Altomare DA;Morishige K;Hayashi M;Sawada K;Ito K;Terai Y;Nishio Y;Klein-Szanto AJ;Burger RA;Ohmichi M;Testa JR;Kimura T
• 通讯作者: Kimura T

An essential role of the HIF-1alpha-c-Myc axis in malignant progression.

HIF-1α-c-Myc 轴在恶性进展中的重要作用。

• 发表时间: 2009
• 期刊: Ann N Y Acad Sci. 1177
• 作者: Yoo YG;Hayashi M;Christensen J;Huang LE.
• 通讯作者: Huang LE.

mTOR is a promising therapeutic target both in cisplatin-sensitive and cisplatin-resistant clear cell carcinoma of the ovary.

• DOI: 10.1158/1078-0432.ccr-09-0365
• 发表时间: 2009-09-01
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Mabuchi S;Kawase C;Altomare DA;Morishige K;Sawada K;Hayashi M;Tsujimoto M;Yamoto M;Klein-Szanto AJ;Schilder RJ;Ohmichi M;Testa JR;Kimura T
• 通讯作者: Kimura T

Requirement of evading apoptosis for HIF-1α-induced malignant progression in mouse cells

• DOI: 10.4161/cc.10.14.16313
• 发表时间: 2011-07-15
• 期刊: CELL CYCLE
• 影响因子: 4.3
• 作者: Hayashi, Masami;Yoo, Yoo Young-Gun;Huang, L. Eric
• 通讯作者: Huang, L. Eric